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Title:
ZWITTERIONIC COMPOUNDS AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/235985
Kind Code:
A1
Abstract:
The present application relates to zwitterion compounds of Formula I, to processes of their preparations, to conjugates thereof, to compositions comprising them and to their use in diagnostics and/or therapy. wherein Q is selected from Q1, Q2, Q3, Q4 and Q5:

Inventors:
PRICE ERIC WILLIAM (CA)
RAHEEM SHVAN JASSIM (CA)
Application Number:
PCT/CA2023/050796
Publication Date:
December 14, 2023
Filing Date:
June 09, 2023
Export Citation:
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Assignee:
UNIV SASKATCHEWAN (CA)
International Classes:
C07C309/14; A61K51/04; A61P35/00; C07D213/55; C07D213/56
Foreign References:
US20090149673A12009-06-11
CN105801688A2016-07-27
US20110151489A12011-06-23
Other References:
L. GUO, Z. TIAN, P.J EDWARDS, Y.L ZHANG, N. SHOBANA, R. JF. ROESKE: "Structure-Activity Studies of GnRH Antagonists Having Dipolar Residues", PEPTIDES : CHEMISTRY, STRUCTURE AND BIOLOGY ; PROCEEDINGS OF THE FOURTEENTH AMERICAN PEPTIDE SYMPOSIUM, JUNE 18 - 23, 1995, COLUMBUS, OHIO, USA, MAYFLOWER SCIENTIFIC, US, vol. 14, 1 January 1996 (1996-01-01) - 23 June 1995 (1995-06-23), US, pages 665 - 666, XP009551403, ISBN: 0-9527011-0-3
Attorney, Agent or Firm:
BERESKIN & PARR LLP/S.E.N.C.R.L., S.R.L. (CA)
Download PDF:
Claims:
CLAIMS: 1. A zwitterion compound of Formula I, or a salt and/or solvate thereof: wherein 5 R1 is H, OH or a protecting group; R2 is OH or a protecting group; Q is selected from Q1, Q2, Q3, Q4 and Q5: Z2 is selected from C1-15alkylene, C2-15alkenylene and C2-15alkynelene, 10 unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R4 and R5 are independently selected from C1-10alkyl, C2-10alkenyl and C2- 10alkynyl; R6 is selected from H, halo, NO2, SO2 and OH; Z1 is selected from C1-15alkylene, C2-15alkenylene and C2-15alkynelene, 5 unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate. 10 2. The compound of claim 1, wherein R1 is H or the protecting group. 3. The compound of claim 1 or 2, wherein R2 is OH or the protecting group. 4. The compound of any one of claims 1 to 3, wherein the protecting group is selected from 9-fluorenenylmethoxycarbonyl (Fmoc), tert-butyloxycarbonyl (Boc), tert-butyl (tBu), trityl (Trt), 2,4-dimethoxybenzyl (Dmb), 9- 15 fluorenylmethyl (Fm) and benzyl (Bn). 5. The compound of claim 4, wherein the protecting group is selected from Fmoc and Boc. 6. The compound of any one of claims 1 to 5, wherein R1 is the protecting group. 20 7. The compound of claim 6, wherein R1 is Fmoc. 8. The compound of any one of claims 1 to 7, wherein R2 is OH. 9. The compound of any one of claims 1 to 8, wherein the compound of Formula I, or a salt and/or solvate thereof, has the following structure:

wherein Q, Z1 and R3 are as defined in claim 1. 10. The compound of any one of claims 1 to 9, wherein R4 and R5 are independently selected from C1-6alkyl, C2-6alkenyl and C2-6alkynyl. 5 11. The compound of claim 10, wherein R4 and R5 are independently selected from CH2CH2CH3, CH(CH3)2, CH2CH3 and CH3. 12. The compound of claim 11, wherein each one of R4 and R5 is CH3. 13. The compound of any one of claims 1 to 9, wherein R6 is H. 14. The compound of any one of claims 1 to 13, wherein Z2 is selected from 10 C1-10alkylene, C2-10alkenylene and C2-10alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 15. The compound of claim 14, wherein Z2 is selected from C1-4alkylene, C2- 4alkenylene and C2-4alkynelene, unsubstituted or substituted with one or 15 more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 16. The compound of claim 15, wherein Z2 is C4alkylene. 17. The compound of claim 15, wherein Z2 is C1alkylene. 18. The compound of any one of claims 1 to 17, wherein Z1 is selected from 20 C1-10alkylene, C2-10alkenylene and C2-10alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 19. The compound of claim 18, wherein Z1 is selected from C1-4alkylene, C2- 4alkenylene and C2-4alkynelene, unsubstituted or substituted with one or 5 more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 20. The compound of claim 19, wherein Z1 is C3alkylene. 21. The compound of any one of claims 1 to 20, wherein R3 is sulfonate. 22. A zwitterionic compound of Formula I, or a salt and/or solvate thereof: 10 wherein R1 is a protecting group; R2 is OH; Q is selected from Q1, Q2, Q3, Q4 and Q5:

Z2 is selected from C1-15alkylene, C2-15alkenylene and C2-15alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently 5 selected from O, N and S; R4 and R5 are independently selected from C1-10alkyl, C2-10alkenyl and C2- 10alkynyl; R6 is selected from H, halo, NO2, SO2 and OH; Z1 is selected from C1-15alkylene, C2-15alkenylene and C2-15alkynelene, 10 unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S; R3 is a sulfonate; provided that when Q is Q1, Q2, Q3 or Q4, then the compound of Formula I is an 15 (R)- or (S)-enantiomer of the carbon to which Z2 is attached. 23. The compound of any one of claims 1 to 22 selected from:

24. A conjugate of formula II, or a salt and/or solvate thereof: wherein Y1 is a complex comprising a chelating agent and one or more radionuclides; Y2 is a targeting ligand; L is a zwitterionic (ZW) linker of the formula (III) wherein Q is selected from Q1, Q2, Q3, Q4 and Q5: Z2 is selected from C1-15alkylene, C2-15alkenylene and C2-15alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R4 and R5 are independently selected from C1-10alkyl, C2-10alkenyl and C2- 10alkynyl; R6 is selected from H, halo, NO2, SO2 and OH; Z1 is selected from C1-15alkylene, C2-15alkenylene and C2-15alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate; and n is an integer 0 to 5.

25. The conjugate of claim 24, wherein R4 and R5 are independently selected from C1-6alkyl, C2-6alkenyl and C2-6alkynyl. 26. The conjugate of claim 25, wherein R4 and R5 are independently selected from CH2CH2CH3, CH(CH3)2, CH2CH3 and CH3. 27. The conjugate of claim 26, wherein each one of R4 and R5 is CH3. 28. The conjugate of claim 24, wherein R6 is H. 29. The conjugate of any one of claims 24 to 28, wherein Z2 is selected from C1-10alkylene, C2-10alkenylene and C2-10alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 30. The conjugate of claim 29, wherein Z2 is C4alkylene. 31. The conjugate of claim 30, wherein Z2 is C1alkylene. 32. The conjugate of any one of claims 24 to 31, wherein Z1 is selected from C1-10alkylene, C2-10alkenylene and C2-10alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 33. The conjugate of claim 32, wherein Z1 is selected from C1-4alkylene, C2- 4alkenylene and C2-4alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 34. The conjugate of claim 33, wherein Z1 is C3alkylene. 35. The conjugate of any one of claims 24 to 34, wherein R3 is sulfonate.

36. The conjugate of any one of claims 24 to 35, wherein the chelating agent is selected from DOTA, NOTA, DTPA, TETA, EDTA, NODAGA, NODASA, TRITA, CDTA, BAT, DFO and HYNIC. 37. The conjugate of claim 36, wherein the chelating agent is DOTA. 38. The conjugate of any one of claims 24 to 37, wherein the one or more radionuclides is selected from 225Ac, 226Ac, 227Ac, 228Ac, 105Ag, 106mAg, 110mAg, 111Ag, 112Ag, 113Ag, 239Am, 240Am, 242Am, 244Am, 37Ar, 71As, 72As, 73As, 74As 76As, 77As, 209At, 210At, 191Au, 192Au, 193Au, 194Au, 195Au, 196Au, 196m2Au, 198Au, 198mAu, 199Au 200mAu, 128Ba, 131Ba, 133mBa, 135mBa, 140Ba, 7Be, 203Bi, 204Bi, 205Bi, 206Bi, 210Bi, 212Bi, 243Bk, 244Bk 245Bk, 246Bk, 248mBk, 250Bk, 76Br, 77Br, 80mBr, 82Br, 11C, 14C, 45Ca, 47Ca, 107Cd, 115Cd, 115mCd 117mCd, 132Ce, 133mCe, 134Ce, 135Ce, 137Ce, 137mCe, 139Ce, 141Ce, 143Ce, 144Ce, 246Cf, 247Cf, 253Cf, 254Cf, 240Cm, 241Cm, 242Cm, 252Cm, 55Co, 56Co, 57Co, 58Co, 58mCo, 60Co, 48Cr, 51Cr, 127Cs, 129Cs 131Cs, 132Cs, 136Cs, 137Cs, 61Cu, 62Cu,64Cu, 67Cu, 153Dy, 155Dy, 157Dy, 159Dy, 165Dy, 166Dy, 160Er 161Er, 165Er, 169Er, 171Er, 172Er, 250Es, 251Es, 253Es, 254Es, 254mEs, 255Es, 256mEs, 145Eu, 146Eu, 147Eu 148Eu, 149Eu, 150mEu, 152mEu, 156Eu, 157Eu, [18F]AIF, 52Fe, 59Fe, 251Fm, 252Fm, 253Fm, 254Fm, 255Fm, 257Fm 66Ga, 67Ga, 68Ga, 72Ga, 73Ga, 146Gd, 147Gd, 149Gd, 151Gd, 153Gd, 159Gd, 68Ge, 69Ge, 71Ge, 77Ge 170Hf, 171Hf, 173Hf, 175Hf, 179m2Hf, 180mHf, 181 Hf, 184Hf, 192Hg, 193Hg, 193mHg, 195Hg, 195mHg, 197Hg 197mHg, 203Hg, 160mHo, 166Ho, 167Ho, 123l, 124l, 126l, 130l, 132l, 133l, 135l, 109ln, 110ln, 111ln, 114mln 115mln, 184lr, 185lr, 186lr, 187lr, 188lr, 189lr, 190lr, 190m2lr, 192lr, 193mlr, 194lr, 194m2lr, 195mlr, 42K, 43K, 76Kr 79Kr, 81mKr, 85mKr, 132La, 133La, 135La, 140La, 141La, 262Lr, 169Lu, 170Lu, 171Lu, 172Lu, 174mLu, 176mLu 177Lu, 177mLu, 179Lu, 257Md, 258Md, 260Md, 28Mg, 52Mn, 90Mo, 93mMo, 99Mo, 100Mo, 13N, 24Na, 90Nb, 91mNb 92mNb, 95Nb, 95mNb, 96Nb, 138Nd, 139mNd, 140Nd, 147Nd, 56Ni, 57Ni, 66Ni, 234Np, 236Np, 99Mo, Np, 238Np 239Np, 150, 1820s, 1830s, 183mOs, 1850s, 189mOs, 1910s, 191mOs, 1930s, 32P, 33P, 228Pa, 229Pa, 230Pa, 232Pa, 233Pa, 234Pa, 200Pb, 201 Pb, 202mPb, 203Pb, 209Pb, 212Pb, 100Pd, 101Pd, 103Pd, 109Pd 111mPd, 112Pd, 143Pm, 148Pm, 148mPm, 149Pm, 151Pm, 204Po, 206Po, 207Po, 210Po, 139Pr, 142Pr, 143Pr, 145Pr, 188Pt, 189Pt, 191Pt, 193mPt, 195mPt, 197Pt, 200Pt, 202Pt, 234Pu, 237Pu, 243Pu, 245Pu, 246Pu, 247Pu 223Ra, 224Ra, 225Ra, 81 Rb, 82Rb, 82mRb, 83Rb, 84Rb, 86Rb, 181 Re, 182Re, 182mRe, 183Re, 184Re, 184mRe, 186Re, 188Re, 189Re, 190mRe, 99Rh, 99mRh, 100Rh, 101mRh, 102Rh, 103mRh, 105Rh, 211Rn, 222Rn, 97Ru, 103Ru, 105Ru, 35S, 118mSb, 119Sb, 120Sb, 120mSb, 122Sb, 124Sb, 126Sb, 127Sb, 128Sb, 129Sb, 43Sc, 44Sc, 44mSc, 46Sc, 47Sc, 48Sc, 72Se, 73Se, 75Se, 153Sm, 156Sm, 110Sn, 113Sn, 117mSn, 119mSn, 121Sn, 123Sn, 125Sn, 82Sr, 83Sr, 85Sr, 89Sr, 91Sr, 173Ta, 175Ta, 176Ta, 177Ta, 180Ta, 182Ta 183Ta, 184Ta, 149Tb, 150Tb, 151Tb, 152Tb, 153Tb, 154Tb, 154mTb, 154m2Tb, 155Tb, 156Tb, 156mTb 156m2Tb, 160Tb, 161Tb, 94Tc, 95Tc, 95mTc, 96Tc, 97mTc, 99mTc, 118Te, 119Te, 119mTe, 121Te, 121mTe, 123mTe, 125mTe, 127Te, 127mTe, 129mTe, 131mTe, 132Te, 227Th, 229Th, 231Th, 234Th, 45Ti, 198TI, 199TI, 200TI, 201TI, 202TI, 204TI, 165Tm, 166Tm, 167Tm, 168Tm, 170Tm, 172Tm, 173Tm, 230U, 231U, 237U, 240U, 48V, 178W, 181W, 185W, 187W, 188W, 122Xe, 125Xe, 127Xe, 129mXe, 131mXe, 133Xe, 133mXe, 135Xe, 85mY, 86Y, 87Y, 87mY, 88Y, 90Y, 90mY, 91 Y, 92Y, 93Y, 166Yb, 169Yb, 175Yb, 62Zn, 65Zn, 69mZn, 71mZn, 72Zn, 86Zr, 88Zr, 89Zr, 95Zr, and 97Zr. 39. The conjugate of claim 38, wherein the radionuclide is selected from 68Ga, 177Lu, [18F]AIF and 90Y. 40. The conjugate of any one of claims 24 to 39, wherein the chelating agent coordinatively bound to two radionuclides. 41. The conjugate of any one of claims 24 to 40, wherein the targeting ligand is selected from an oligonucleotide, an oligopeptide, a protein, a peptide and a small molecule compound. 42. The conjugate of claim 41, wherein the targeting ligand is a tumor-targeting ligand. 43. The conjugate of claim 42, wherein the targeting ligand is selected from TATE, TOC and PSMA.

44. The conjugate of any one of claims 24 to 43, wherein n is an integer 1 to 3. 45. The conjugate of claim 44, wherein n is 1. 46. The conjugate of claim 44, wherein n is 2. 47. The conjugate of any one of claims 24 to 46, wherein the conjugate comprises a spacer. 48. The conjugate of claim 47, wherein the conjugate has the formula IIa wherein, S is a spacer. 49. The conjugate of claim 48, wherein the spacer is polyethylene glycol (PEG). 50. The conjugate of claim 49, wherein the PEG spacer contains four PEG units. 51. A conjugate of Formula IV, or a salt and/or solvate thereof: wherein Y1 is a complex comprising a chelating agent and one or more radionuclides, wherein the chelating agent is desferrioxamine (DFO) or a compound of the following formula;

wherein R7, R8, R9 and R10 are independently selected from H and C1-4alkyl; each a, c and e is an integer independently selected from 3, 4, 5, 6 and 7; each b and d is an integer independently selected from 1, 2, 3 and 4; L1 is a linker group R11 is selected from C1-10alkyl and C1-6alkylenephenyl, optionally substituted by one of NH2, OH, SH, N3, CO2H and , wherein X is O, S or NH; R12, R13, R14, R15 and R16 are independently selected from H and C1-4alkyl; f is an integer selected from 1, 2, 3 and 4; each g, l and k is an integer independently selected from 3, 4, 5, 6 and 7; each h and j is an integer independently selected from 1, 2, 3 and 4; Y2 is a targeting ligand; S1 is a biomolecule conjugating group; L is a zwitterionic (ZW) linker of the formula

ĨIII) wherein Q is selected from Q1, Q2, Q3, Q4 and Q5: Z2 is selected from C1-15alkylene, C2-15alkenylene and C2-15alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R4 and R5 are independently selected from C1-10alkyl, C2-10alkenyl and C2- 10alkynyl; R6 is selected from H, halo, NO2, SO2 and OH; Z1 is selected from C1-15alkylene, C2-15alkenylene and C2-15alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate; n is an integer 1 to 5; wherein the chelating agent is a compound of Formula V, Y1 is attached to L at R11 of L1 group , and the L is further optionally attached to one to three additional L groups, or the L is attached between the Y3 and L1 groups of Y1, or one L is attached at R11 of L1 group and another L is attached between the Y3 and L1 groups of Y1, and each one of the L is further optionally attached to one to three additional L groups; and wherein the chelating agent is DFO, the point of attachment of L is at the amine and wherein the * indicates the point of attachment. 52. The conjugate of claim 51, wherein R4 and R5 are independently selected from C1-6alkyl, C2-6alkenyl and C2-6alkynyl. 53. The conjugate of claim 52, wherein R4 and R5 are independently selected from CH2CH2CH3, CH(CH3)2, CH2CH3 and CH3. 54. The conjugate of claim 53, wherein each one of R4 and R5 is CH3. 55. The conjugate of claims 51, wherein R6 is H.

56. The conjugate of any one of claims 51 to 55, wherein Z2 is selected from C1-10alkylene, C2-10alkenylene and C2-10alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 57. The conjugate of claim 56, wherein Z2 is C4alkylene. 58. The conjugate of claim 56, wherein Z2 is C1alkylene. 59. The conjugate of any one of claims 51 to 58, wherein Z1 is selected from C1-10alkylene, C2-10alkenylene and C2-10alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 60. The conjugate of claim 59, wherein Z1 is selected from C1-4alkylene, C2- 4alkenylene and C2-4alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S. 61. The conjugate of claim 60, wherein Z1 is C3alkylene. 62. The conjugate of any one of claims 51 to 61, wherein R3 is sulfonate. 63. The conjugate of claim 51, wherein L is selected from

64. The conjugate of claim 63, wherein L is or . 65. The conjugate of any one of claims 51 to 64, wherein the chelating agent is DFO. 66. The conjugate of any one of claims 51 to 64, wherein the chelating agent is a compound of Formula V, wherein at least one of R7, R8, R9 and R10 is C1-2alkyl.

67. The conjugate of claim 66, wherein R7 is CH3 and each one of R8, R9 and R10 is H. 68. The conjugate of claim 66 or 67, wherein each a, c and e is an integer independently selected from 4, 5 and 6. 69. The conjugate of claim 68, wherein a, c and e are 5. 70. The conjugate of any one of claims 66 to 69, wherein each b and d is an integer independently selected from 1, 2 and 3. 71. The conjugate of claim 70, wherein b and d are 2. 72. The conjugate of any one of claims 64 to 71, wherein f is selected from the integer 1, 2 and 3. 73. The conjugate of claim 72, wherein f is 2. 74. The conjugate of any one of claims 64 to 73, wherein when Y is , R12 is selected from H and C1-2alkyl. 75. The conjugate of claim 74, wherein R12 is selected from H and CH3. 76. The conjugate of any one of claims 64 to 73, wherein when Y is , R13, R14, R15 and R16 are independently selected from H and C1-2alkyl. 77. The conjugate of claim 76, wherein at least one of R13, R14, R15 and R16 is C1-2alkyl. 78. The conjugate of claim 77, wherein R16 is CH3 and each one of R13, R14 and R15 is H.

79. The conjugate of any one of claims 76 to 78, wherein each g, l and k is an integer independently selected from 4, 5 and 6. 80. The conjugate of claim 79, wherein g, l and k are 5. 81. The conjugate of any one of claims 76 to 80, wherein each h and j is an integer independently selected from 1, 2 and 3. 82. The conjugate of claim 81, wherein h and j are 2. 83. The conjugate of any one of claims 64 to 82, wherein a, c and e are 5 and b and d are 2 and the compound of Formula V has the following structure: 84. The conjugate of claim 83, wherein Y3 is , g, i and k are 5 and h and j are 2 and the compound of Formula V has the following structure: (V). 85. The conjugate of claim 64, wherein the compound of Formula V is selected from

86.The conjugate of any one of claims 51 to 85, wherein n is an integer 1 to 3.

87. The conjugate of any one of claims 51 to 86, wherein the chelating agent is a compound of Formula V and Y1 is attached to L at R11 of L1 group . 88. The conjugate of claim 87, wherein L is further optionally attached to one or two additional L groups. 89. The conjugate of any one of claims 51 to 86, wherein the chelating agent is a compound of Formula V and L is attached between the Y3 and L1 groups of Y1. 90. The conjugate of claim 89, wherein L is further optionally attached to one ot two additional L groups. 91. The conjugate of any one of claims 51 to 86, wherein the chelating agent is a compound of Formula V and one L is attached at R11 of L1 group , and another L is attached between the Y3 and L1 groups of Y1. 92. The conjugate of claim 91, wherein L group attached at R11 of L1 group is further attached to one to three additional L groups.

93. The conjugate of claim 91, wherein the chelating agent is DFO, the point of attachment of L is at the amine . 94. The conjugate of any one of claims 51 to 92, wherein the Y1-L is selected from DFO- I-(R)-PZ3; DFO- I-(S)-PZ3;

95. The conjugate of any one of claims 51 to 94, wherein S1 is a biomolecule conjugating group selected from NH2, OH, SH, N3, CO2H, ONH2, NHNH2, C(O)C1-4alkyl, C≡CH, SCN, C(O)NH2, NHC(X)NH2, C1-4alkyleneN3, NHC(O)C1-4alkyleneN3, NHC(O)C1-4alkyleneONH2, NHC(O)C1- 4alkyleneNHNH2, NHC(O)OC1-4alkyleneN3, C(O)NHC1-4alkylene- phenylene-tetrazine, and , wherein represents a single or a double bond and X is O, S or NH. 96. The conjugate of claim 95, wherein the biomolecule conjugating group is , wherein X is O, S or NH. 97. The conjugate of claim 96, wherein the biomolecule conjugating group is 98. The conjugate of any one of claims 51 to 97, wherein the one or more radionuclides is selected from 225Ac, 226Ac, 227Ac, 228Ac, 105Ag, 106mAg, 110mAg, 111Ag, 112Ag, 113Ag, 239Am, 240Am, 242Am, 244Am, 37Ar, 71As, 72As, 73As, 74As 76As, 77As, 209At, 210At, 191Au, 192Au, 193Au, 194Au, 195Au, 196Au, 196m2Au, 198Au, 198mAu, 199Au 200mAu, 128Ba, 131Ba, 133mBa, 135mBa, 140Ba, 7Be, 203Bi, 204Bi, 205Bi, 206Bi, 210Bi, 212Bi, 243Bk, 244Bk 245Bk, 246Bk, 248mBk, 250Bk, 76Br, 77Br, 80mBr, 82Br, 11C, 14C, 45Ca, 47Ca, 107Cd, 115Cd, 115mCd 117mCd, 132Ce, 133mCe, 134Ce, 135Ce, 137Ce, 137mCe, 139Ce, 141Ce, 143Ce, 144Ce, 246Cf, 247Cf, 253Cf, 254Cf, 240Cm, 241Cm, 242Cm, 252Cm, 55Co, 56Co, 57Co, 58Co, 58mCo, 60Co, 48Cr, 51Cr, 127Cs, 129Cs 131Cs, 132Cs, 136Cs, 137Cs, 61Cu, 62Cu,64Cu, 67Cu, 153Dy, 155Dy, 157Dy, 159Dy, 165Dy, 166Dy, 160Er 161Er, 165Er, 169Er, 171Er, 172Er, 250Es, 251Es, 253Es, 254Es, 254mEs, 255Es, 256mEs, 145Eu, 146Eu, 147Eu 148Eu, 149Eu, 150mEu, 152mEu, 156Eu, 157Eu, [18F]AIF, 52Fe, 59Fe, 251Fm, 252Fm, 253Fm, 254Fm, 255Fm, 257Fm 66Ga, 67Ga, 68Ga, 72Ga, 73Ga, 146Gd, 147Gd, 149Gd, 151Gd, 153Gd, 159Gd, 68Ge, 69Ge, 71Ge, 77Ge 170Hf, 171Hf, 173Hf, 175Hf, 179m2Hf, 180mHf, 181 Hf, 184Hf, 192Hg, 193Hg, 193mHg, 195Hg, 195mHg, 197Hg 197mHg, 203Hg, 160mHo, 166Ho, 167Ho, 123l, 124l, 126l, 130l, 132l, 133l, 135l, 109ln, 110ln, 111ln, 114mln 115mln, 184lr, 185lr, 186lr, 187lr, 188lr, 189lr, 190lr, 190m2lr, 192lr, 193mlr, 194lr, 194m2lr, 195mlr, 42K, 43K, 76Kr 79Kr, 81mKr, 85mKr, 132La, 133La, 135La, 140La, 141La, 262Lr, 169Lu, 170Lu, 171Lu, 172Lu, 174mLu, 176mLu 177Lu, 177mLu, 179Lu, 257Md, 258Md, 260Md, 28Mg, 52Mn, 90Mo, 93mMo, 99Mo, 100Mo, 13N, 24Na, 90Nb, 91mNb 92mNb, 95Nb, 95mNb, 96Nb, 138Nd, 139mNd, 140Nd, 147Nd, 56Ni, 57Ni, 66Ni, 234Np, 236Np, 99Mo, Np, 238Np 239Np, 150, 1820s, 1830s, 183mOs, 1850s, 189mOs, 1910s, 191mOs, 1930s, 32P, 33P, 228Pa, 229Pa, 230Pa, 232Pa, 233Pa, 234Pa, 200Pb, 201 Pb, 202mPb, 203Pb, 209Pb, 212Pb, 100Pd, 101Pd, 103Pd, 109Pd 111mPd, 112Pd, 143Pm, 148Pm, 148mPm, 149Pm, 151Pm, 204Po, 206Po, 207Po, 210Po, 139Pr, 142Pr, 143Pr, 145Pr, 188Pt, 189Pt, 191Pt, 193mPt, 195mPt, 197Pt, 200Pt, 202Pt, 234Pu, 237Pu, 243Pu, 245Pu, 246Pu, 247Pu 223Ra, 224Ra, 225Ra, 81 Rb, 82Rb, 82mRb, 83Rb, 84Rb, 86Rb, 181 Re, 182Re, 182mRe, 183Re, 184Re, 184mRe, 186Re, 188Re, 189Re, 190mRe, 99Rh, 99mRh, 100Rh, 101mRh, 102Rh, 103mRh, 105Rh, 211Rn, 222Rn, 97Ru, 103Ru, 105Ru, 35S, 118mSb, 119Sb, 120Sb, 120mSb, 122Sb, 124Sb, 126Sb, 127Sb, 128Sb, 129Sb, 43Sc, 44Sc, 44mSc, 46Sc, 47Sc, 48Sc, 72Se, 73Se, 75Se, 153Sm, 156Sm, 110Sn, 113Sn, 117mSn, 119mSn, 121Sn, 123Sn, 125Sn, 82Sr, 83Sr, 85Sr, 89Sr, 91Sr, 173Ta, 175Ta, 176Ta, 177Ta, 180Ta, 182Ta 183Ta, 184Ta, 149Tb, 150Tb, 151Tb, 152Tb, 153Tb, 154Tb, 154mTb, 154m2Tb, 155Tb, 156Tb, 156mTb 156m2Tb, 160Tb, 161Tb, 94Tc, 95Tc, 95mTc, 96Tc, 97mTc, 99mTc, 118Te, 119Te, 119mTe, 121Te, 121mTe, 123mTe, 125mTe, 127Te, 127mTe, 129mTe, 131mTe, 132Te, 227Th, 229Th, 231Th, 234Th, 45Ti, 198TI, 199TI, 200TI, 201TI, 202TI, 204TI, 165Tm, 166Tm, 167Tm, 168Tm, 170Tm, 172Tm, 173Tm, 230U, 231U, 237U, 240U, 48V, 178W, 181W, 185W, 187W, 188W, 122Xe, 125Xe, 127Xe, 129mXe, 131mXe, 133Xe, 133mXe, 135Xe, 85mY, 86Y, 87Y, 87mY, 88Y, 90Y, 90mY, 91 Y, 92Y, 93Y, 166Yb, 169Yb, 175Yb, 62Zn, 65Zn, 69mZn, 71mZn, 72Zn, 86Zr, 88Zr, 89Zr, 95Zr, and 97Zr. 99. The conjugate of any one of claims 51 to 98, wherein the targeting ligand is selected from an oligonucleotide, an oligopeptide, a protein, a peptide and a small molecule compound. 100. A composition comprising a conjugate of any one of claims 51 to 99 and a carrier. 101. A pharmaceutical composition comprising a conjugate of any one of claims 51 to 99 and a pharmaceutically acceptable carrier. 102. The pharmaceutical composition of claim 101, wherein the composition is a diagnostic composition. 103. The pharmaceutical composition of claim 101, wherein the composition is a theranostic composition. 104. A method of medical diagnosing comprising administering an effective amount of a conjugate of any one of claims 24 to 99 or a composition of claim 101 to a subject in need thereof. 105. The method of claim 104, wherein the medical diagnostic method is performed using positron emission tomography (PET), single-photon emission computed tomography (SPECT), radioisotope renography or scintigraphy. 106. A method of treatment of one or more diseases, disorders or conditions, comprising administering an effective amount of a conjugate of any one of claims 24 to 99 or a composition of claim 101 to a subject in need thereof.

107. A method of radionuclide therapy comprising administering an effective amount of a conjugate of any one of claims 24 to 99 or a composition of claim 101 to a subject in need thereof. 108. A method of theranostic treatment comprising administering an effective amount of a conjugate of any one of claims 24 to 99 or a composition of claim 101 to a subject in need thereof. 109. The method any one of claims 104 to 108, wherein the method is for treating one or more diseases, disorders or conditions associated with cellular proliferation. 110. The method any one of claims 104 to 108, wherein the method is for treating one or more of cancers, thyroid diseases (e.g., hyperthyroidism or thyrotoxicosis), blood disorders (e.g., Polycythemia vera, an excess of red blood cells produced in the bone marrow), and/or cellular proliferation in blood vessels following balloon angioplasty and/or stent placement (known as restenosis). 111. The method of claim 110, wherein the method is for treating cancer. 112. The method of claim 111, wherein the cancer is adrenal cancer, bladder cancer, blood cancer, bone cancer, brain cancer, breast cancer, carcinoma, cervical cancer, colon cancer, colorectal cancer, corpus uterine cancer, ear, nose and throat (ENT) cancer, endometrial cancer, esophageal cancer, gastrointestinal cancer, head and neck cancer, Hodgkin's disease cancer, intestinal cancer, kidney cancer, larynx cancer, leukemia, liver cancer, lymph node cancer, lymphoma, lung cancer, melanoma, mesothelioma, myeloma, nasopharynx cancer, neuroblastoma, non-Hodgkin's lymphoma, oral cancer, ovarian cancer, pancreatic cancer, penile cancer, pharynx cancer, prostate cancer, rectal cancer, sarcomcancer, seminomcancer, skin cancer, stomach cancer, teratomcancer, testicular cancer, thyroid cancer, uterine cancer, vaginal cancer, vascular tumor cancer, and/or cancer from metastases thereof. 113. Use of a conjugate of any one of claims 24 to 99 or a composition of claim 101 in the manufacture of a medicament for medical diagnosis. 114. Use of a conjugate of any one of claims 24 to 99 or a composition of claim 101 in the manufacture of a medicament for treatment of one or more diseases, disorders or conditions. 115. Use of a conjugate of any one of claims 24 to 99 or a composition of claim 101 in the manufacture of a medicament for theranostic applications. 116. Use of a conjugate of any one of claims 24 to 99 or a composition of claim 101 in the manufacture of a medicament for radionuclide therapy. 117. The use of any one of claims 113 to 116, wherein the use is for treating one or more diseases, disorders or conditions associated with cellular proliferation. 118. The use of any one of claims 113 to 116, wherein the use is for treating one or more of cancers, thyroid diseases (e.g., hyperthyroidism or thyrotoxicosis), blood disorders (e.g., Polycythemia vera, an excess of red blood cells produced in the bone marrow), and/or cellular proliferation in blood vessels following balloon angioplasty and/or stent placement (known as restenosis). 119. The use of claim 118, wherein the use for treating cancer. 120. The use of claim 119, wherein the cancer is adrenal cancer, bladder cancer, blood cancer, bone cancer, brain cancer, breast cancer, carcinoma, cervical cancer, colon cancer, colorectal cancer, corpus uterine cancer, ear, nose and throat (ENT) cancer, endometrial cancer, esophageal cancer, gastrointestinal cancer, head and neck cancer, Hodgkin's disease cancer, intestinal cancer, kidney cancer, larynx cancer, leukemia, liver cancer, lymph node cancer, lymphoma, lung cancer, melanoma, mesothelioma, myeloma, nasopharynx cancer, neuroblastoma, non-Hodgkin's lymphoma, oral cancer, ovarian cancer, pancreatic cancer, penile cancer, pharynx cancer, prostate cancer, rectal cancer, sarcomcancer, seminomcancer, skin cancer, stomach cancer, teratomcancer, testicular cancer, thyroid cancer, uterine cancer, vaginal cancer, vascular tumor cancer, and/or cancer from metastases thereof. 121. A kit comprising a compound of claims 1 to 23 or a conjugate of any one of claims 24 to 99 or a composition of claim 101 and a pharmaceutically acceptable excipient. 122. The kit of claim 121 for use in medical diagnosis. 123. The kit of claim 121 for use in radionuclide therapy. 124. The kit of claim 121 for use in theranostic applications.

Description:
ZWITTERIONIC COMPOUNDS AND USES THEREOF RELATED APPLICATION [0001] This application claims the benefit of priority to United States Provisional Application No. 63/350,598, filed June 9, 2022, the contents of which are incorporated herein by reference in its entirety. FIELD [0002] The present application relates to zwitterionic compounds and their use, for example, as linkers to form radiopharmaceuticals. BACKGROUND [0003] Non-invasive molecular imaging (MI) and radionuclide therapy is revolutionizing the ability to apply the principles of personalized medicine in the diagnosis, treatment, and monitoring of diseases such as, for example, cancer [9]. The field of molecular imaging encompasses a number of imaging modalities, including single photon emission computed tomography (SPECT, nuclear), positron emission tomography (PET, nuclear), magnetic resonance imaging (MRI, non-nuclear), and optical imaging (visible and near-infrared dyes – non-nuclear). Molecular imaging, particularly when multiple modalities are integrated (e.g. PET/CT, PET/optical/CT, PET/MRI) enables specific, quantitative, real-time, and non-invasive investigation of biochemical activities at the cellular and sub-cellular level (effectively a limited full-body biopsy through imaging). Each radiopharmaceutical agent is tailored to specific receptors and disease states towards precision (personalized) medicine. [0004] For example, cancer-targeting peptides can be transformed into molecular imaging or radiotherapeutic agents through attachment to a positron-emitting ( β + ) radionuclide (e.g. [ 68 Ga]Ga 3+ , [ 18 F]AlF) for pre-therapy PET scans and patient selection, followed by high-energy particle-emitting radionuclides (e.g. [ 177 Lu]Lu 3+ ) for peptide- receptor radionuclide-therapy (PRRT) [10-12]. The cancer-targeting peptide provides site- specific delivery and accumulation of the peptide and the attached radioactive “payload” to a molecular target such as a receptor, which is over-expressed on tumour cells (Figure 1A) [13]. An exemplary application of this is the somatostatin (SSTR) receptor-targeting peptide — Tyr 3 -octreotate “TATE” — which is employed in the recently FDA-approved PRRT agent [ 177 Lu]Lu-DOTA-TATE. This PRRT agent only shows therapeutic efficacy if the patient’s cancer (e.g. neuroendocrine tumours) expresses high levels of the SSTR receptor. [0005] PET is a technique able to visualize the tumour-receptor heterogeneity of all lesions simultaneously, unlike a biopsy which only takes a small sample of a single (and often heterogeneous) tumour. PET enables the clinical identification and stratification of patients based on the status of many therapeutically relevant receptors, depending on the cancer-targeting peptide used [14]. This method can identify tumours which lack sufficient expression of the target receptor and accurately predict response to follow-up PRRT [14]. PET is used to confirm receptor target accessibility in the personalized medicine development [15, 16]. [0006] A successful example of a peptide-agent is the PET radiopharmaceutical [ 68 Ga]Ga-DOTA-TATE (DOTA-Tyr 3 -octreotate, DOTA = radiometal chelator). It has been used for many years in Europe as an accurate method for detecting and staging neuroendocrine tumours/cancer, and this agent was FDA approved in 2016 in the USA under the name NetSpot® [17]. DOTA-TATE “gallium PET scans” replaced OctreoScan SPECT imaging as the standard of care due to its superior ability to detect cancerous lesions [18]. Therapeutic analogues of DOTA-TATE using the therapeutic radiometals lutetium-177 and yttrium-90 (high energy electron, β- emitters) have been used in Germany in thousands of patients successfully [10, 19]. The PRRT agent [ 177 Lu]Lu- DOTA-TATE was FDA approved as “Lutathera” in January 2018. There is a knowledge- gap in the understanding of how changes in the chemical structure of peptide-based radiopharmaceuticals affect their biological behavior. These effects include unsuitable pharmacokinetics, poor tumour retention, and high retention in and subsequent irradiation of healthy tissues. Peptide-linkers and kidney uptake [0007] The effect that the chemical properties of “linkers” have on the overall behavior of radiopharmaceuticals is poorly understood, but it is generally known that: 1) increasing the space between radiometal chelator and peptide-agent with a linker can restore binding affinity in cases where it is lost due to steric interference, and 2) modulating polarity by adding in varying numbers of charged amino acids (e.g. aspartic acid) or short and polar polymers (e.g. polyethylene glycol (PEG)) can impart drastic changes on pharmacokinetics and tissue clearance [20-25]. [0008] As to why radiolabeled peptides “stick” in the kidneys, it has been suggested that after glomerular filtration in the kidneys, low molecular weight proteins (e.g. radioactive peptides) that remain in the ultrafiltrate, bind to endocytic receptors at the luminal surface of proximal tubular cells in the renal cortex (not the glomeruli or distal tubules) [26, 27]. This process is followed by internalization, transfer to lysosomes, proteolytic degradation, and finally retention of radiometal [26]. Normally, the broken- down peptide is transported back into the blood stream as amino acids, but radiometals are residualizing and remain trapped in the tubular cell lysosomes, causing them to become “stuck” where they deliver high radiation dose to the kidney tubules and glomeruli. Although the exact receptors and mechanisms responsible for tubular reabsorption of peptides are not fully understood, the receptor megalin (and associated receptor cubilin) has been identified as a scavenger receptor with the function of non-specific uptake of charged proteins and has high expression in the proximal tubules of the kidneys [28, 29]. This suggests that megalin-cubilin could be one of the causes of radiopeptide retention in the kidneys. It has been experimentally shown that comparing radiolabeled peptides (including several derivatives of octreotide and octreotate) in both healthy and megalin- deficient mice demonstrated a dramatic decrease in kidney uptake in megalin-deficient mice (~2-3 fold) [26]. Peptide derivatives of [ 111 In]In-DTPA-octreotide with positive, neutral, and negative net charges have also confirmed high kidney retention, with positive charges showing more severe retention [30]. [0009] A method used clinically to reduce kidney uptake of radiolabeled peptides has been the co-infusion of amino acids such as lysine and glutamic acid [31, 32]. Specifically, lysine has been found to primarily block uptake of positively charged peptides [33], and glutamic acid to reduce the uptake of negatively charged peptides [34]. It has been demonstrated that kidney uptake was correlated with the number of charged amino acids, with positively charged amino acids appearing to play a role due to the negative surface charge of proximal tubular cells [34]. These co-infusions reduced kidney uptake of radiolabeled peptides by ~10-50%, but also resulted in severe nausea in ~50% of patients [33]. The ability to reduce kidney uptake of the radioactive peptides, rather than using a nausea-inducing cocktail of amino acids, would improve patient comfort. Amino acid charge interactions are clearly involved in kidney uptake and retention, and it appears that the charge-distribution over the surface of proteins also has an effect on uptake [34- 36]. [0010] Although not for the purpose of blocking kidney uptake, permanent zwitterions (ZW) have been shown to minimize non-specific “sticking” of near-infrared dyes in vivo [1, 2]. Reduction of non-specific uptake and retention of radiolabeled peptides in excretory organs (e.g. kidneys) and other healthy tissues would reduce radioactive background, therefore improving PET imaging contrast and therapeutic index of radionuclide therapy agents. Reduced uptake and retention in healthy tissues would also reduce radiation toxicity and would be very desirable. Research and clinical translation of peptide-based radiopharmaceuticals has been rapidly expanding for both cancer and infectious disease, and a modular approach to reducing uptake and retention in kidney, spleen, and other healthy tissues would be of great utility [37, 38]. [0011] A zwitterion is a molecule possessing both a positive and a negative charge simultaneously at a certain pH. Most amino acid molecules form zwitterions at physiological pH, but not when incorporated into peptides and proteins. In recent years, a number of peer-reviewed publications have featured the concept of incorporating synthetic permanent zwitterions to increase polarity and reduce sticking to solid surfaces. These typically utilize quaternary amines for permanent positive charge, and often use sulfonate (R-SO3-) groups for negative charge at most physiologically relevant pH values. The conjugate acid of an alkyl sulfonate is the alkyl sulfonic acid, which have pKa values between -7 to 0, meaning they are deprotonated and negatively charged above pH 0 (physiological pH ~5.5-7.5). Fluorescent dyes from Frangioni et al incorporate permanent zwitterions into their structure and promote improved pharmacokinetics and increased polarity [1-4]. Some nanoparticles have utilized permanent zwitterions on their surfaces to improve water solubility, reduce protein corona formation, and to reduce sticking to solid surfaces [5-8]. In 2020, a patent (US 10,710,962, Zwitterionic Reagents) was issued to Siemens Healthcare Diagnostics for a range of permanent zwitterion structures that could be used to coat or incorporate into solid surfaces (e.g. test tubes, membranes, pipets tips) to reduce adherence and sticking of things such as proteins and other molecules. SUMMARY [0012] The present application discloses zwitterionic (ZW) compounds, which can be used as modular linkers to form radiopharmaceuticals, for example, for diagnostics and/or therapy. The modularity of linkers enables fast incorporation into radiopharmaceuticals and improve pharmacokinetics and tissue clearance of the radiopharmaceuticals. [0013] Accordingly the present application includes a zwitterion compound of Formula I, or a salt and/or solvate thereof: wherein R 1 is H, OH or a protecting group; R 2 is OH or a protecting group; Q is selected from Q1, Q2, Q3, Q4 and Q5: Z 2 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 4 and R 5 are independently selected from C 1-10 alkyl, C 2-10 alkenyl and C 2-10 alkynyl; R 6 is selected from one or more of H, halo, NO 2 , SO 2 and OH; Z 1 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate. [0014] The present application also includes a conjugate of Formula II, or a salt and/or solvate thereof: wherein Y 1 is a complex comprising a chelating agent and one or more radionuclides; Y 2 is a targeting ligand; L is a zwitterionic (ZW) linker of the formula (III) wherein Q is selected from Q1, Q2, Q3, Q4 and Q5:

Z 2 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 4 and R 5 are independently selected from C 1-10 alkyl, C 2-10 alkenyl and C 2-10 alkynyl; R 6 is selected from H, halo, NO 2 , SO 2 and OH; Z 1 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate; and n is an integer 0 to 5. [0015] The present application also includes a conjugate of Formula IV, or a salt and/or solvate thereof: wherein Y 1 is a complex comprising a chelating agent and one or more radionuclides, wherein the chelating agent is desferrioxamine (DFO) or a compound of the following formula; wherein R 7 , R 8 , R 9 and R 10 are independently selected from H and C 1-4 alkyl; each a, c and e is an integer independently selected from 3, 4, 5, 6 and 7; each b and d is an integer independently selected from 1, 2, 3 and 4; L 1 is a linker group Y 3 is or R 11 is selected from C 1-10 alkyl and C 1-6 alkylenephenyl, optionally substituted by one of NH 2 , OH, SH, N 3 , CO 2 H and , wherein X is O, S or NH; R 12 , R 13 , R 14 , R 15 and R 16 are independently selected from H and C 1-4 alkyl; f is an integer selected from 1, 2, 3 and 4; each g, l and k is an integer independently selected from 3, 4, 5, 6 and 7; each h and j is an integer independently selected from 1, 2, 3 and 4; Y 2 is a targeting ligand; S 1 is a biomolecule conjugating group; L is a zwitterionic (ZW) linker of the formula (III) wherein Q is selected from Q1, Q2, Q3, Q4 and Q5: Z 2 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 4 and R 5 are independently selected from C 1-10 alkyl, C 2-10 alkenyl and C 2-10 alkynyl; R 6 is selected from H, halo, NO 2 , SO 2 and OH; Z 1 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate; n is an integer 1 to 5; wherein the chelating agent is a compound of Formula V, Y 1 is attached to L at R 11 of L 1 group , and the L is further optionally attached to one to three additional L groups, or the L is attached between the Y 3 and L 1 groups of Y 1 , or one L is attached at R 11 of L 1 group and another L is attached between the Y 3 and L 1 groups of Y 1 , and each one of the L is further optionally attached to one to three additional L groups; and wherein the chelating agent is DFO, the point of attachment of L is at the amine and wherein the * indicates the point of attachment. [0016] The present application also includes a composition comprising a conjugate of the application and a carrier. The present application also includes a pharmaceutical composition comprising a conjugate of the application and a pharmaceutically acceptable carrier. In an embodiment, the composition of the application is a diagnostic or a theranostic composition. [0017] The conjugates of the application are useful in medical diagnosis, diagnosing, treatment of one or more diseases, disorders or conditions, radionuclide therapy and/or theranostic treatments. Accordingly, the present application includes a method of diagnosing, treatment of one or more diseases, disorders or conditions, radionuclide treatment and/or theranostic treatments, comprising administering an effective amount of a conjugate of the application to a subject in need thereof. [0018] The present application also includes a kit comprising a compound, a conjugate or a composition of the application. [0019] Other features and advantages of the present application will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating embodiments of the application, are given by way of illustration only and the scope of the claims should not be limited by these embodiments but should be given the broadest interpretation consistent with the description as a whole. DRAWINGS [0020] The embodiments of the application will now be described in greater detail with reference to the attached drawings in which: [0021] Figure 1 shows the structural and conceptual introduction to A) peptide- based molecular imaging agents, peptide-receptor radionuclide-therapy (PRRT) agents, “linkers”, and B) the chemical structures of common “linkers”. [0022] Figure 2 shows the structure of FDA approved NetSpot radiotracer, unlabelled DOTA-Tyr 3 -octreotate (TATE) (Top), and labelled [ 68 Ga]Ga-DOTA-TATE (Bottom). [0023] Figure 3 shows the structure of unlabeled exemplary DOTA-Zwitterion(ZW)- PEG4-TATE (Top), and labelled exemplary [ 68 Ga]Ga-DOTA-ZW-PEG4-TATE (Bottom) with improved tumor-tissue ratios and faster pharmacokinetic of healthy-tissue clearance. [0024] Figure 4 shows the structure of two exemplary embedded ZW units in unlabelled DOTA-(ZW) 2 -PEG4-TATE (Top), and exemplary labelled [ 68 Ga]Ga-DOTA- (ZW) 2 -PEG4-TATE (Bottom) with improved tumor-tissue ratios and faster pharmacokinetic of healthy-tissue clearance. [0025] Figure 5 shows representative radio-HPLC chromatograms for human serum stability study of exemplary [ 68 Ga]Ga-DOTA-Lys(ZW)-PEG4-TATE at gradient of MeCN:H 2 O (both with 0.1% FA) with 0.5 mL/min flow rate. [0026] Figure 6 shows representative radio-HPLC chromatograms for mouse serum stability study of exemplary [ 68 Ga]Ga-DOTA-Lys(ZW)-PEG4-TATE at gradient of MeCN:H 2 O (both with 0.1% FA) with 0.65 mL/min flow rate. [0027] Figure 7 shows representative radio-HPLC chromatograms for human serum stability study of exemplary [ 68 Ga]Ga-DOTA-Lys(ZW) 2 -PEG4-TATE at gradient of MeCN:H 2 O (both with 0.1% FA) with 0.5 mL/min flow rate. [0028] Figure 8 shows representative radio-HPLC chromatograms for mouse serum stability study of exemplary [ 68 Ga]Ga-DOTA-Lys(ZW) 2 -PEG4-TATE at gradient of MeCN:H 2 O (both with 0.1% FA) with 0.65 mL/min flow rate. [0029] Figure 9 shows representative radio-HPLC chromatograms for human serum stability study of exemplary [ 68 Ga]Ga-DOTA-Pyr(ZW)-PEG4-TATE at gradient of MeCN:H 2 O (both with 0.1% FA) with 0.65 mL/min flow rate. [0030] Figure 10 shows representative radio-HPLC chromatograms for mouse serum stability study of exemplary [ 68 Ga]Ga-DOTA-Pyr(ZW)-PEG4-TATE at gradient of MeCN:H 2 O (both with 0.1% FA) with 0.65 mL/min flow rate. [0031] Figure 11 shows 90 minutes dynamic PET-CT imaging of 5-6 MBq of comparative [ 68 Ga]Ga-DOTA-TATE (Top), exemplary [ 68 Ga]Ga-DOTA-Lys(ZW)-PEG4- TATE (Middle) and exemplary [ 68 Ga]Ga-DOTA-Lys(ZW) 2 -PEG4-TATE (Bottom) in healthy female CD1 mice (n = 4) in 200 µL of sterile saline with less than 10% ethanol content injected intravenously via tail vein catheter, under isoflurane anesthesia (2.5%, 2-2.5 L/min). [0032] Figure 12 shows dynamic PET/CT imaging (0-90 minutes) of 5-6 MBq of exemplary [ 68 Ga]Ga-DOTA-Pyr(ZW)-PEG4-TATE in healthy female (top) and male (bottom) CD1 mice (n = 4) injected intravenously via tail vein catheter in 200 µL of sterile saline with less than 10% ethanol content, under isoflurane anesthesia (2.5%, 2-2.5 L/min). [0033] Figure 13 shows the time-activity curve (TAC) from 5-6 MBq of [ 68 Ga]Ga- comparative DOTA-TATE and exemplary ZW-bearing derivatives in healthy CD1 mice with the quantity of radioactivity in the kidneys displayed over time, with data extracted from dynamic PET/CT imaging (0-90 minutes) by contouring the organ of interest (OOI). [0034] Figure 14 shows the results of the ex vivo biodistribution study from the injection of 5-6 MBq (~200 µL, sterile saline, <10% ethanol) of comparative [ 68 Ga]Ga- DOTA-TATE and exemplary ZW-bearing derivatives in healthy CD1 mice two hours post injection (top) and the same data displayed with expanded Y-axis revealing the uptake differences in other healthy organs (bottom). Significance was measured using Student’s one-tail and two-tail t-tests, *p < 0.05, **p < 0.01, ***p < 0.001, ns (not significant). [0035] Figure 15 shows dynamic PET/CT imaging (0-90 minutes) following injection of 5-6 MBq of comparative [ 68 Ga]Ga-DOTA-TATE (top) and exemplary [ 68 Ga]Ga- DOTA-Lys(ZW)-PEG4-TATE (bottom) in male NSG mice (n = 3) in 200 µL of sterile saline with less than 10% ethanol content injected intravenously via tail vein catheter, under isoflurane anesthesia (2%, 2-2.5 L/min). [0036] Figure 16 shows time-activity curve (TAC) from 5-6 MBq of comparative [ 68 Ga]Ga-DOTA-TATE and exemplary [ 68 Ga]Ga-DOTA-Lys(ZW)-PEG4-TATE, and [ 68 Ga]Ga-DOTA-Glu-PEG4-TATE in NOD/SCID mice bearing subcutaneous AR42J xenografts with the quantity of radioactivity in the kidneys and tumors displayed over time, with data extracted from dynamic PET/CT imaging (0-90 minutes) by contouring the organ of interest (OOI). [0037] Figure 17 shows the results of the biodistribution study from injection of 5-6 MBq of comparative [ 68 Ga]Ga-DOTA-TATE and exmplary [ 68 Ga]Ga-DOTA-Lys(ZW)- PEG4-TATE, and [ 68 Ga]Ga-DOTA-Lys(ZW) 2 -PEG4-TATE in male NSG mice bearing subcutaneous xenografts (AR42J) two hours post injection (left) and the same data displayed with an expanded Y-axis revealing the uptake in other healthy organs (right). Significance was measured using Student’s t-tests with one tail and two tail, *P < 0.05, **P < 0.01, ***P < 0.001, ns (not significant). [0038] Figure 18 shows structure of one exemplary embedded Pyr(ZW)-PZW units in unlabelled DOTA-PZW-PEG4-TATE (Top), and exemplary labelled [ 68 Ga]Ga-DOTA- PZW-PEG4-TATE (Bottom). PZW=Pyr(ZW). [0039] Figure 19 shows representative radio-HPLC chromatograms for mouse serum stability study of exemplary [ 68 Ga]Ga-DOTA-Pyr(ZW)-PEG4-TATE at gradient of MeCN:H 2 O (both with 0.1% FA) with 0.65 mL/min flow rate [0040] Figure 20 shows representative radio-HPLC chromatograms for human serum stability study of exemplary [ 68 Ga]Ga-DOTA-Pyr(ZW)-PEG4-TATE at gradient of MeCN:H 2 O (both with 0.1% FA) with 0.65 mL/min flow rate. DESCRIPTION OF VARIOUS EMBODIMENTS Definitions [0041] Unless otherwise indicated, the definitions and embodiments described in this and other sections are intended to be applicable to all embodiments and aspects of the present application herein described for which they are suitable as would be understood by a person skilled in the art. [0042] The term “comprising” and its derivatives, as used herein, are intended to be open ended terms that specify the presence of the stated features, elements, components, groups, integers, and/or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and/or steps. The foregoing also applies to words having similar meanings such as the terms, “including”, “having” and their derivatives. [0043] The term “consisting” and its derivatives, as used herein, are intended to be closed terms that specify the presence of the stated features, elements, components, groups, integers, and/or steps, but exclude the presence of other unstated features, elements, components, groups, integers and/or steps. [0044] The term “consisting essentially of”, as used herein, is intended to specify the presence of the stated features, elements, components, groups, integers, and/or steps as well as those that do not materially affect the basic and novel characteristic(s) of features, elements, components, groups, integers, and/or steps. [0045] Terms of degree such as “substantially”, “about” and “approximately” as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the word it modifies. [0046] As used in this application, the singular forms “a”, “an” and “the” include plural references unless the content clearly dictates otherwise. [0047] In embodiments comprising an “additional” or “second” component, the second component as used herein is chemically different from the other components or first component. A “third” component is different from the other, first, and second components, and further enumerated or “additional” components are similarly different. [0048] The term “and/or” as used herein means that the listed items are present, or used, individually or in combination. In effect, this term means that “at least one of” or “one or more” of the listed items is used or present. [0049] The term “suitable” as used herein means that the selection of the particular compound or conditions would depend on the specific synthetic manipulation to be performed, the identity of the molecule(s) to be transformed and/or the specific use for the compound, but the selection would be well within the skill of a person trained in the art. All process/method steps described herein are to be conducted under conditions sufficient to provide the product shown. A person skilled in the art would understand that all reaction conditions, including, for example, reaction solvent, reaction time, reaction temperature, reaction pressure, reactant ratio and whether or not the reaction should be performed under an anhydrous or inert atmosphere, can be varied to optimize the yield of the desired product and it is within their skill to do so. [0050] The present application refers to a number of chemical terms and abbreviations used by those skilled in the art. Nevertheless, definitions of selected terms are provided for clarity and consistency. [0051] The products of the processes of the application may be isolated according to known methods, for example, the compounds may be isolated by evaporation of the solvent, by filtration, centrifugation, chromatography or other suitable method. [0052] One skilled in the art will recognize that where a reaction step of the present application is carried out in a variety of solvents or solvent systems, said reaction step may also be carried out in a mixture of the suitable solvents or solvent systems. [0053] The term “chelating agent” as used herein includes molecules that form stable complexes with traceable metal atoms under physiological conditions such that the metal remains bound in vivo. For diagnostic imaging purposes, “chelating agent” or “bifunctional chelating agent” is a compound which has a reactive functional group to facilitate conjugation with a targeting ligand such as a peptide or antibody, and chelating moieties for labeling by a radionuclide and, on binding to a radionuclide metal, forms a complex that is stable under physiological conditions. [0054] The term “targeting ligand” as used herein is a molecule or part of a molecule that binds with specificity to another molecule. The targeting ligand can be a tissue specific and/or organ and/or a receptor specific moiety. Thus, the targeting ligand can bind or attach to one or more tissues, organs and/or receptors. The targeting ligand can be any such molecule known to those of ordinary skill in the art. The binding may be by any mechanism of binding known to those of ordinary skill in the art. [0055] The term “compound(s) of the application” or “compound(s) of the present application”, and the like, as used herein refers to a compound of Formula I or a salt and/or solvate thereof. [0056] The term “conjugate(s) of the application” or “conjugate(s) of the present application”, and the like, as used herein refers to a chelator-linker-targeting peptide conjugate compound of Formula II or a salt and/or solvate thereof. [0057] The term “composition(s) of the application” or “composition(s) of the present application, and the like, as used herein refers to a composition comprising one or more conjugates of the application and a carrier. [0058] The term “alkyl” as used herein, whether it is used alone or as part of another group, means straight or branched chain, saturated alkyl groups. The number of carbon atoms that are possible in the referenced alkyl group are indicated by the prefix “Cn1-n2”. For example, the term C 1-10 alkyl means an alkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. All alkyl groups are optionally fluoro-substituted unless otherwise indicated. [0059] The term “alkenyl” as used herein, whether it is used alone or as part of another group, means straight or branched chain, unsaturated alkyl groups containing at least one double bond. The number of carbon atoms that are possible in the referenced alkylene group are indicated by the prefix “Cn1-n2”. For example, the term C 2-6 alkenyl means an alkenyl group having 2, 3, 4, 5 or 6 carbon atoms and at least one double bond. All alkenyl groups are optionally fluoro-substitued unless otherwise indicated. [0060] The term “alkynyl” as used herein, whether it is used alone or as part of another group, means straight or branched chain, unsaturated alkynyl groups containing at least one triple bond. The number of carbon atoms that are possible in the referenced alkyl group are indicated by the prefix “Cn1-n2”. For example, the term C 2-6 alkynyl means an alkynyl group having 2, 3, 4, 5 or 6 carbon atoms. [0061] The term “alkylene”, whether it is used alone or as part of another group, means straight or branched chain, saturated alkylene group, that is, a saturated carbon chain that contains substituents on two of its ends. The number of carbon atoms that are possible in the referenced alkylene group are indicated by the prefix “Cn1-n2”. For example, the term C 1-10 alkylene means an alkylene group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. All alkyl groups are optionally fluorosubstituted unless otherwise indicated. [0062] The term “alkenylene” as used herein, whether it is used alone or as part of another group, means straight or branched chain, unsaturated alkenylene groups containing at least one double bond and substituents on two of its ends. The number of carbon atoms that are possible in the referenced alkenylene group are indicated by the prefix “Cn1-n2”. For example, the term C 2-6 alkenylene means an alkenylene group having 2, 3, 4, 5 or 6 carbon atoms and at least one double bond. All alkenylene groups are optionally fluoro-substitued unless otherwise indicated. [0063] The term “alkynylene” as used herein, whether it is used alone or as part of another group, means straight or branched chain, unsaturated alkynylene groups containing at least one triple bond and substituents on two of its ends. The number of carbon atoms that are possible in the referenced alkynylene group are indicated by the prefix “Cn1-n2”. For example, the term C 2-6 alkynylene means an alkynylene group having 2, 3, 4, 5 or 6 carbon atoms. [0064] The term “halogen” (or “halo”) whether it is used alone or as part of another group, refers to a halogen atom and includes fluoro, chloro, bromo and iodo. [0065] The term “heteromoiety” refers to heteroatoms and includes O, S and NH. [0066] The term "substituted" refers to the addition of a substituent group to a parent compound. [0067] The term “interrupted” refers to the insertion of a moiety between two carbon atoms. Non-limiting examples of such atoms and moieties include —O—, —S—, — N(H)—. [0068] The term “protecting group” or “PG” and the like as used herein refers to a chemical moiety which protects or masks a reactive portion of a molecule to prevent side reactions in those reactive portions of the molecule, while manipulating or reacting a different portion of the molecule. After the manipulation or reaction is complete, the protecting group is removed under conditions that do not degrade or decompose the remaining portions of the molecule. The selection of a suitable protecting group can be made by a person skilled in the art. Many conventional protecting groups are known in the art, for example as described in “Protective Groups in Organic Chemistry” McOmie, J.F.W. Ed., Plenum Press, 1973, in Greene, T.W. and Wuts, P.G.M., “Protective Groups in Organic Synthesis”, John Wiley & Sons, 3 rd Edition, 1999 and in Kocienski, P. Protecting Groups, 3rd Edition, 2003, Georg Thieme Verlag (The Americas). [0069] The term “anion containing group” as used herein refers to a group with negatively charged ion. [0070] The term “zwitterion” or “zwitterionic” refers to a molecule possessing both a positive and negative charge simultaneously at a certain pH, and isolation. The total net charge of the chemical compound is zero (electrically neutral). A zwitterionic moiety which in itself may possess a net charge of zero may be incorporated into a larger molecule such as a chelator-linker-peptide conjugate which as a whole may possess a net charge other than zero. [0071] The symbol “ ” when drawn perpendicularly across a bond indicates a point of attachment of the group. [0072] The term “subject” as used herein includes all members of the animal kingdom, while members of the animal kingdom include mammals, and suitably refer to humans. Thus, the methods and uses of the present application are applicable to human therapy and veterinary therapy. [0073] The term “cell” as used herein refers to a single cell or a plurality of cells and includes a cell either in a cell culture or in a subject. [0074] The term “pharmaceutically acceptable” means compatible with the treatment of subjects, for example humans. [0075] The term “pharmaceutically acceptable carrier” means a non-toxic solvent, dispersant, excipient, adjuvant or other material which is mixed with the active ingredient in order to permit the formation of a pharmaceutical composition, i.e., a dosage form capable of administration to a subject. [0076] The term “pharmaceutically acceptable salt” means either an acid addition salt or a base addition salt which is suitable for, or compatible with the treatment of subjects. [0077] An acid addition salt suitable for, or compatible with, the treatment of subjects is any non-toxic organic or inorganic acid addition salt of any basic compound. [0078] A base addition salt suitable for, or compatible with, the treatment of subjects is any non-toxic organic or inorganic base addition salt of any acidic compound. [0079] The term “solvate” as used herein means a compound, or a salt and/or prodrug of a compound, wherein molecules of a suitable solvent are incorporated in the crystal lattice. A suitable solvent is physiologically tolerable at the dosage administered. [0080] The term “treating” or “treatment” as used herein and as is well understood in the art, means an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired clinical results can include, but are not limited to alleviation or amelioration of one or more symptoms or conditions, diminishment of extent of disease, stabilized (i.e. not worsening) state of disease, preventing spread of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, diminishment of the reoccurrence of disease, and remission (whether partial or total), whether detectable or undetectable. “Treating” and “treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment. “Treating” and “treatment” as used herein also include prophylactic treatment. For example, a subject with early cancer can be treated to prevent progression, or alternatively a subject in remission can be treated with a compound or composition of the application to prevent recurrence. Treatment methods comprise administering to a subject a therapeutically effective amount of one or more of the compounds of the application and optionally consist of a single administration, or alternatively comprise a series of administrations. [0081] The term “theranostic application” as used herein means using one radioactive drug to diagnose and treat a condition of choice, typically with the radioactive drug remaining identical while the radionuclide being changed (e.g. gallium-68 for PET imaging, lutetium-177 for therapy). [0082] The term "therapeutic treatment" as used herein can include a treatment administered to a subject in need of imaging. The subject can be in need of imaging to aid in diagnosis; to locate a position for a therapeutic intervention; to assess the functioning of a body part; and/or to assess the presence or absence of a condition. The effectiveness of a therapeutic imaging treatment can be confirmed based on the capture of an image sufficient for its intended purpose. [0083] The term “administered” as used herein means administration of a therapeutically effective amount of a compound, or one or more compounds, or a composition of the application to a cell or a subject. [0084] The term “radionuclide” as used herein means an atom with an unstable nucleus, which undergoes radioactive decay, resulting in the emission of gamma ray(s) or subatomic particles such as positrons, alpha or beta particles, or Auger electrons. These emissions constitute ionizing radiation. Radionuclides occur naturally, or can be produced artificially. [0085] The term “spacer” as used herein means an entity which increases the space between the chelating agent complex and the targeting ligand. The spacer can restore binding affinity in cases where it is lost due to steric interference. [0086] The term “biomolecule conjugating group” as used herein means a functional group that reacts with a functional group in a targeting ligand to form a covalent bond. [0087] The term “Positron Emission Tomography (PET)” as used herein means a functional imaging technique applied in nuclear medicine, whereby a three-dimensional image (e.g. of functional processes) in the body is produced. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide, which is introduced into the body in form of a pharmaceutical compound. [0088] The term Single-Photon Emission Computed Tomography (SPECT)” as used herein means a three-dimensional diagnostic imaging technique using gamma rays emitted by radioisotopes. In contrast with PET, the tracer used in SPECT emits gamma radiation that is measured directly, whereas a PET tracer emits positrons that annihilate with near-by electrons, which are a few millimeters away, causing two gamma photons to be emitted in opposite directions. [0089] The term “DMF” as used herein means dimethylformamide. [0090] The term “Fmoc” as used herein means fluorenylmethoxycarbonyl protecting group. [0091] The term “DCM” as used herein means dichloromethane. [0092] The term “TIPS” as used herein means triisopropylsilane. [0093] The term “TFA” as used herein means trifluoroacetic acid. Compounds and Compositions of the Application [0094] Therefore, the present application includes a zwitterion compound of Formula I, or a salt and/or solvate thereof: wherein R 1 is H, OH or a protecting group; R 2 is OH or a protecting group; Q is selected from Q1, Q2, Q3, Q4 and Q5: Z 2 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S; R 4 and R 5 are independently selected from C 1-10 alkyl, C 2-10 alkenyl and C 2-10 alkynyl; R 6 is selected from H, halo, NO 2 , SO 2 and OH; Z 1 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S; R 3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate. [0095] In some embodiments, R 1 is H or the protecting group. [0096] In some embodiments, R 2 is OH or the protecting group. [0097] Protecting group used in the present application can be any protecting group known in the art. In some embodiments, the protecting group is selected from 9- fluorenenylmethoxycarbonyl (Fmoc), tert-butyloxycarbonyl (Boc), tert-butyl ( t Bu), trityl (Trt), 2,4-dimethoxybenzyl (Dmb), 9-fluorenylmethyl (Fm) and benzyl (Bn). In some embodiments, the protecting group is selected from Fmoc and Boc. [0098] In some embodiments, R 1 is the protecting group. In some embodiments, R 1 is Fmoc. [0099] In some embodiments, R 2 is OH. [00100] In some embodiments, R 1 is Fmoc, R 2 is OH and the compound of Formula I has the following structure: or a salt and/or solvate thereof, wherein Q, Z 1 and R 3 are as defined for Formula I. [00101] In some embodiments, Q is Q1, , and the compound of Formula I has the following structure: or a salt and/or solvate thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , Z 1 and Z 2 are as defined for Formula I. [00102] In some embodiments, Q is Q2, , and the compound of Formula I has the following structure:

or a salt and/or solvate thereof, wherein R 1 , R 2 , R 3 , R 6 , Z 1 and Z 2 are as defined for Formula I. [00103] In some embodiments, Q is Q3, , and the compound of Formula I has the following structure:

or a salt and/or solvate thereof, wherein R 1 , R 2 , R 3 , R 6 , Z 1 and Z 2 are as defined for Formula I. [00104] In some embodiments, Q is Q4, , and the compound of Formula I has the following structure: or a salt and/or solvate thereof, wherein R 1 , R 2 , R 3 , R 6 , Z 1 and Z 2 are as defined for Formula I. [00105] In some embodiments, Q is Q5, , and the compound of Formula I has the following structure:

or a salt and/or solvate thereof, wherein R 1 , R 2 , R 3 , R 6 and Z 1 are as defined for Formula I. [00106] In some embodiments, when Q is (Q1), (Q2), (Q3) or (Q4), the stereochemistry at the carbon to which Z 2 is bonded is either R or S. Therefore, in some embodiments, Q1 is

or ; Q2 is or ; Q3 is or and Q4 is or . [00107] In some embodiments, the stereochemistry at the carbon to which Z 2 is attached is R. In some embodiments, the stereochemistry at the carbon to which Z 2 is attached is S. [00108] In some embodiments, R 4 and R 5 are independently selected from C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl. In some embodiments, R 4 and R 5 are independently selected from C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl. In some embodiments, R 4 and R 5 are independently selected from CH 2 CH 2 CH 3 , C(CH 3 ) 3 , CH(CH 3 )CH 2 CH 3 and CH 2 CH(CH 3 ) 2 , CH(CH 3 ) 2 , CH 2 CH 3 and CH 3 . In some embodiments, R 4 and R 5 are independently selected from CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 and CH 3 . In some embodiments, at least one of R 4 and R 5 is CH 3 . In some embodiments, each one of R 4 and R 5 is CH 3 . [00109] In some embodiments, R 6 is H. [00110] In some embodiments, Z 2 is selected from C 1-10 alkylene, C 2-10 alkenylene and C 2-10 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2- 6 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is selected from C 1-4 alkylene, C 2-4 alkenylene and C 2- 4 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is C 1-4 alkylene. In some embodiments, Z 2 is C4alkylene. In some embodiments, Z 2 is C1alkylene. [00111] In some embodiments, Z 1 is selected from C 1-10 alkylene, C 2-10 alkenylene and C 2-10 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2- 6alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is selected from C 1-4 alkylene, C 2-4 alkenylene and C 2- 4alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is C 3 alkylene. [00112] In some embodiments, R 3 is sulfonate. [00113] In some embodiments, the zwitterion compound of Formula I, or a salt and/or solvate thereof:

wherein R 1 is a protecting group; R 2 is OH; Q is selected from Q1, Q2, Q3, Q4 and Q5: Z 2 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S; R 4 and R 5 are independently selected from C 1-10 alkyl, C 2-10 alkenyl and C 2-10 alkynyl; R 6 is selected from H, halo, NO 2 , SO 2 and OH; Z 1 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S; R 3 is sulfonate; provided that when Q is Q1, Q2, Q3 or Q4, then the compound of formula I is an (R)- or (S)-enantiomer of the carbon to which Z 2 is attached. In some embodiments, the compound of Formula I is selected from

[00114] The present application further includes a conjugate of Formula II, or a salt and/or solvate thereof: wherein Y 1 is a complex comprising a chelating agent and one or more radionuclides; Y 2 is a targeting ligand; L is a zwitterion (ZW) linker of the formula wherein Q is selected from Q1, Q2, Q3, Q4 and Q5: Z 2 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S; R 4 and R 5 are independently selected from C 1-10 alkyl, C 2-10 alkenyl and C 2-10 alkynyl; R 6 is selected from H, halo, NO 2 , SO 2 and OH; Z 1 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S; R 3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate; and n is an integer 0 to 5. [00115] In some embodiments, Q is Q1, , and the compound of Formula II has the following structure: or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 4 , R 5 , Z 1 , Z 2 and n are as defined for Formula II. [00116] In some embodiments, Q is Q2, , and the compound of Formula II has the following structure:

or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 6 , Z 1 , Z 2 and n are as defined for Formula II. [00117] In some embodiments, Q is Q3, , and the compound of Formula II has the following structure:

or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 6 , Z 1 , Z 2 and n are as defined for Formula II. [00118] In some embodiments, Q is Q4, , and the compound of Formula II has the following structure: or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 6 , Z 1 , Z 2 and n are as defined for Formula II. [00119] In some embodiments, Q is Q5, , and the compound of Formula II has the following structure:

or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 6 , Z 1 and n are as defined for Formula II. [00120] In some embodiments, when Q is (Q1), (Q2), (Q3) or (Q4), the stereochemistry at the carbon to which Z 2 is bonded is either R or S. In some embodiments, the stereochemistry at the carbon to which Z 2 is attached is R. In some embodiments, the stereochemistry at the carbon to which Z 2 is attached is S. [00121] In some embodiments, R 4 and R 5 are independently selected from C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl. In some embodiments, R 4 and R 5 are independently selected from C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl. In some embodiments, R 4 and R 5 are independently selected from CH 2 CH 2 CH 3 , C(CH 3 ) 3 , CH(CH 3 )CH 2 CH 3 and CH 2 CH(CH 3 ) 2 , CH(CH 3 ) 2 , CH 2 CH 3 and CH 3 . In some embodiments, R 4 and R 5 are independently selected from CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 and CH 3 . In some embodiments, at least one of R 4 and R 5 is CH 3 . In some embodiments, each one of R 4 and R 5 is CH 3 . [00122] In some embodiments, R 6 is H. [00123] In some embodiments, Z 2 is selected from C 1-10 alkylene, C 2-10 alkenylene and C 2-10 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2- 6 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is selected from C 1-4 alkylene, C 2-4 alkenylene and C 2- 4 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is C4alkylene. In some embodiments, Z 2 is C1alkylene. [00124] In some embodiments, Z 1 is selected from C 1-10 alkylene, C 2-10 alkenylene and C 2-10 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2- 6alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is selected from C 1-4 alkylene, C 2-4 alkenylene and C 2- 4 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is C 3 alkylene. [00125] In some embodiments, R 3 is sulfonate. [00126] In some embodiments, the complex comprising a chelating agent and one or more radionuclides is a coordination complex, in which the one or more radionuclides are coordinatively bound to the chelating agent. [00127] In some embodiments, the chelating agent is selected from DOTA, NOTA, DTPA, TETA, EDTA, NODAGA, NODASA, TRITA, CDTA, BAT, DFO and HYNIC. In some embodiments, the chelating agent is DOTA. [00128] In some embodiments, the radionuclide is selected from a transition metal, rare-earth metal, lanthanide, actinide and metalloid. [00129] Radionuclides that can be used in the present application include but are not limited to the following elements and their isotopes: 225 Ac, 226 Ac, 227 Ac, 228 Ac, 105 Ag, 106m Ag, 110m Ag, 111 Ag, 112 Ag, 113 Ag, 239 Am, 240 Am, 242 Am, 244 Am, 37 Ar, 71 As, 72 As, 73 As, 74 As 76 As, 77 As, 209 At, 210 At, 191 Au, 192 Au, 193 Au, 194 Au, 195 Au, 196 Au, 196m2 Au, 198 Au, 198m Au, 199 Au 200m Au, 128 Ba, 131 Ba, 133m Ba, 135m Ba, 140 Ba, 7 Be, 203 Bi, 204 Bi, 205 Bi, 206 Bi, 210 Bi, 212 Bi, 243 Bk, 244 Bk 245 Bk, 246 Bk, 248m Bk, 250 Bk, 76 Br, 77 Br, 80m Br, 82 Br, 11 C, 14 C, 45 Ca, 47 Ca, 107 Cd, 115 Cd, 115 mCd 117m Cd, 132 Ce, 133m Ce, 134 Ce, 135 Ce, 137 Ce, 137m Ce, 139 Ce, 141 Ce, 143 Ce, 144 Ce, 246 Cf, 247 Cf, 253 Cf, 254 Cf, 240 Cm, 241 Cm, 242 Cm, 252 Cm, 55 Co, 56 Co, 57 Co, 58 Co, 58m Co, 60 Co, 48 Cr, 51 Cr, 127 Cs, 129 Cs 131 Cs, 132 Cs, 136 Cs, 137 Cs, 61 Cu, 62 Cu, 64 Cu, 67 Cu, 153 Dy, 155 Dy, 157 Dy, 159 Dy, 165 Dy, 166 Dy, 160 Er 161 Er, 165 Er, 169 Er, 171 Er, 172 Er, 250 Es, 251 Es, 253 Es, 254 Es, 254m Es, 255 Es, 256m Es, 145 Eu, 146 Eu, 147 Eu 148 Eu, 149 Eu, 150m Eu, 152m Eu, 156 Eu, 157 Eu, [ 18 F]AIF, 52 Fe, 59 Fe, 251 Fm, 252 Fm, 253 Fm, 254 Fm, 255 Fm, 257 Fm 66 Ga, 67 Ga, 68 Ga, 72 Ga, 73 Ga, 146 Gd, 147 Gd, 149 Gd, 151 Gd, 153 Gd, 159 Gd, 68 Ge, 69 Ge, 71 Ge, 77 Ge 170 Hf, 171 Hf, 173 Hf, 175 Hf, 179m2 Hf, 180m Hf, 181 Hf, 184 Hf, 192 Hg, 193 Hg, 193m Hg, 195 Hg, 195m Hg, 197 Hg 197m Hg, 203 Hg, 160m Ho, 166 Ho, 167 Ho, 123 l, 124 l, 126 l, 130 l, 132 l, 133 l, 135 l, 109 ln, 110 ln, 111 ln, 114m ln 115m ln, 184 lr, 185 lr, 186 lr, 187 lr, 188 lr, 189 lr, 190 lr, 190m2 lr, 192 lr, 193m lr, 194 lr, 194m2 lr, 195m lr, 42 K, 43 K, 76 Kr 79 Kr, 81m Kr, 85m Kr, 132 La, 133 La, 135 La, 140 La, 141 La, 262 Lr, 169 Lu, 170 Lu, 171 Lu, 172 Lu, 174m Lu, 176m Lu 177 Lu, 177m Lu, 179 Lu, 257 Md, 258 Md, 260 Md, 28 Mg, 52 Mn, 90 Mo, 93m Mo, 99 Mo, 100 Mo, 13 N, 24 Na, 90 Nb, 91m Nb 92m Nb, 95 Nb, 95m Nb, 96 Nb, 138 Nd, 139m Nd, 140 Nd, 147 Nd, 56 Ni, 57 Ni, 66 Ni, 234 Np, 236 Np, 99 Mo, Np, 238 Np 239 Np, 15 0, 182 0s, 183 0s, 183m Os, 185 0s, 189m Os, 191 0s, 191m Os, 193 0s, 32 P, 33 P, 228 Pa, 229 Pa, 230 Pa, 232 Pa, 233 Pa, 234 Pa, 200 Pb, 201 Pb, 202 mPb, 203 Pb, 209 Pb, 212 Pb, 100 Pd, 101 Pd, 103 Pd, 109 Pd 111m Pd, 112 Pd, 143 Pm, 148 Pm, 148m Pm, 149 Pm, 151 Pm, 204 Po, 206 Po, 207 Po, 210 Po, 139 Pr, 142 Pr, 143 Pr, 145 Pr, 188 Pt, 189 Pt, 191 Pt, 193m Pt, 195m Pt, 197 Pt, 200 Pt, 202 Pt, 234 Pu, 237 Pu, 243 Pu, 245 Pu, 246 Pu, 247 Pu 223 Ra, 224 Ra, 225 Ra, 81 Rb, 82 Rb, 82 mRb, 83 Rb, 84 Rb, 86 Rb, 181 Re, 182 Re, 182m Re, 183 Re, 184 Re, 184m Re, 186 Re, 188 Re, 189 Re, 190m Re, 99 Rh, 99m Rh, 100 Rh, 101m Rh, 102 Rh, 103m Rh, 105 Rh, 211 Rn, 222 Rn, 97 Ru, 103 Ru, 105 Ru, 35 S, 118m Sb, 119 Sb, 120 Sb, 120m Sb, 122 Sb, 124 Sb, 126 Sb, 127 Sb, 128 Sb, 129 Sb, 43 Sc, 44 Sc, 44m Sc, 46 Sc, 47 Sc, 48 Sc, 72 Se, 73 Se, 75 Se, 153 Sm, 156 Sm, 110 Sn, 113 Sn, 117m Sn, 119m Sn, 121 Sn, 123 Sn, 125 Sn, 82 Sr, 83 Sr, 85 Sr, 89 Sr, 91 Sr, 173 Ta, 175 Ta, 176 Ta, 177 Ta, 180 Ta, 182 Ta 183 Ta, 184 Ta, 149 Tb, 150 Tb, 151 Tb, 152 Tb, 153 Tb, 154 Tb, 154m Tb, 154m2 Tb, 155 Tb, 156 Tb, 156m Tb 156m2 Tb, 160 Tb, 161 Tb, 94 Tc, 95 Tc, 95m Tc, 96 Tc, 97m Tc, 99m Tc, 118 Te, 119 Te, 119m Te, 121 Te, 121m Te, 123m Te, 125m Te, 127 Te, 127m Te, 129m Te, 131m Te, 132 Te, 227 Th, 229 Th, 231 Th, 234 Th, 45 Ti, 198 TI, 199 TI, 200 TI, 201 TI, 202 TI, 204 TI, 165 Tm, 166 Tm, 167 Tm, 168 Tm, 170 Tm, 172 Tm, 173 Tm, 230 U, 231 U, 237 U, 240 U, 48 V, 178 W, 181 W, 185 W, 187 W, 188 W, 122 Xe, 125 Xe, 127 Xe, 129m Xe, 131m Xe, 133 Xe, 133m Xe, 135 Xe, 85m Y, 86 Y, 87 Y, 87m Y, 88 Y, 90 Y, 90m Y, 91 Y, 92 Y, 93 Y, 166 Yb, 169 Yb, 175 Yb, 62 Zn, 65 Zn, 69m Zn, 71m Zn, 72 Zn, 86 Zr, 88 Zr, 89 Zr, 95 Zr, and 97 Zr and the like. The skilled person would understand that any other radionuclide known in the art can also be used in the conjugate of the present application. [00130] In some embodiment, the radionuclide is selected from 68 Ga, 177 Lu, [ 18 F]AIF and 90 Y. [00131] In some embodiments, the conjugate of the present application comprises the chelating agent coordinatively bound to two radionuclides. In some embodiments, one radionuclide is diagnostically active and second radionuclide is therapeutically active. In some embodiments, the diagnostically active radionuclide is selected from 68 Ga and [ 18 F]AIF. In some embodiments, the therapeutically active radionuclide is selected from 177 Lu and 90 Y. [00132] In some embodiments, the targeting ligand is a receptor specific moiety. In some embodiments, the targeting ligand is selective of specific for a cell surface molecule expressed on the surface of a target cell. In some embodiments, the targeting ligand is selective or specific for the targeted organ or tissue. In some embodiments, the targeting ligand of the present application directing the conjugate of the present application to a targeted tissue, organ, receptor or other biologically expressed composition. [00133] Examples of targeting ligands include, without limiting, proteins, peptides and peptidomimetics such as arginine-glycine-aspartic acid (RGD)-containing peptides and peptidomimetics, amino-acid sequences, antibodies or fragments thereof such as Fab fragments and antigen binding sites of antibodies, single-chain variable fragments of antibodies, nucleotide sequences, DNA sequences, RNA sequences, peptide nucleic acid (PNA) sequences, carbohydrates, and steroids. In some embodiments, the targeting ligand is selected from an oligonucleotide, an oligopeptide, a protein, a peptide and a small molecule compound. [00134] Examples of targeting ligands include, without limiting, gemtuzumab, inotuumab, trastuzumab (Herceptin), HD37, M195, LMB2, lym1, 8106, HMFG1, CC49, rituximab, epratuzumab, lorvotuzumab, 2C 3 , imgn388, SAR3419, BilB062, brentixumab, glembatumumab, SGN-75, PSMA ADC, ASG-5ME or mdx-1203. In some embodiments, the targeting antibody is a variant of gemtuzumab, inotuumab, trastuzumab (Herceptin), HD37, M195, LMB2, lym1, 8106, HMFG1, CC49, rituximab, epratuzumab, lorvotuzumab, 2C 3 , imgn388, SAR3419, BilB062, brentixumab, glembatumumab, SGN-75, PSMA ADC, ASG-5ME, mdx-1203, TATE, TOC, PSMA, bombesin derivatives (e.g. RM2, BBN and the like), FAPI derivatives, and the like. A person skilled in the art would understand that any other targeting ligands known in the art can also be used in the conjugate of the present application. [00135] In some embodiments, the targeting ligand is a tumor-targeting ligand. In some embodiments, the tumor-targeting ligand is selective or specific for a molecular target such as a receptor. [00136] In some embodiments, the targeting ligand is selected from TATE, TOC and PSMA. [00137] In some embodiments, n is an integer 1 to 3. In some embodiments, n is 1. In some embodiments, n is 2. As such, the conjugate of the present application comprises at least one ZW linker. In some embodiments, the conjugate of the present application comprises two ZW linkers. [00138] In some embodiments, the targeting ligand and the complex comprising the chelating agent form a covalent bond with the ZW linker to form the conjugate. The ZW linker is a permanent zwitterionic group which possesses both a positive and a negative charge simultaneously. In some embodiments, the permanent zwitterionic group is formed at physiological pH of 5.5-7.5. [00139] In some embodiments, the ZW linker is a natural or unnatural amino acid with a primary amine. In some embodiments, the natural amino acid is lysine. In some embodiments, the unnatural amino acid is pyridyl-alanine. [00140] In some embodiments, the conjugate of the present application further comprises a spacer. The spacer used in the conjugate of the application can be any spacer known in the art. Examples include, but are not limited to, poly(ethylene)glycol (PEG) and hexanoic acid. In some embodiments, the spacer is poly(ethylene)glycol. Therefore, when the conjugate of the present application comprises a spacer, the conjugate has the formula IIa: wherein, S is a spacer. [00141] The length of the spacer of the present application is defined by the number of the repeating PEG units. In some embodiments, PEG spacer contains 2 to 15 polyethylene glycol units. In some embodiments, PEG contains four units. [00142] In some embodiments, the conjugate of the present application is a radiopharmaceutical. In some embodiments, the radiopharmaceutical is a protein-based radiopharmaceutical. In some embodiments, the radiopharmaceutical is a peptide-based radiopharmaceutical. [00143] In some embodiments, the conjugate of the present application has a greater solubility and/or higher stability in vivo than [ 68 Ga]Ga-DOTA-TATE. [00144] In some embodiments, the conjugate of the present application has lower kidney and other healthy organ uptake and/or retention than [ 68 Ga]Ga-DOTA-TATE. [00145] The present application further includes a conjugate of Formula IV, or a salt and/or solvate thereof: wherein Y 1 is a complex comprising a chelating agent and one or more radionuclides, wherein the chelating agent is desferrioxamine (DFO) or a compound of the following formula; wherein R 7 , R 8 , R 9 and R 10 are independently selected from H and C 1-4 alkyl; each a, c and e is an integer independently selected from 3, 4, 5, 6 and 7; each b and d is an integer independently selected from 1, 2, 3 and 4; L 1 is a linker group ; Y 3 is or ; R 11 is selected from C 1-10 alkyl and C 1-6 alkylenephenyl, optionally substituted by one of NH 2 , OH, SH, N 3 , CO 2 H and , wherein X is O, S or NH; R 12 , R 13 , R 14 , R 15 and R 16 are independently selected from H and C 1-4 alkyl; f is an integer selected from 1, 2, 3 and 4; each g, l and k is an integer independently selected from 3, 4, 5, 6 and 7; each h and j is an integer independently selected from 1, 2, 3 and 4; Y 2 is a targeting ligand; S 1 is a biomolecule conjugating group; L is a zwitterionic (ZW) linker of the formula (III) wherein Q is selected from Q1, Q2, Q3, Q4 and Q5:

Z 2 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 4 and R 5 are independently selected from C 1-10 alkyl, C 2-10 alkenyl and C 2-10 alkynyl; R 6 is selected from H, halo, NO 2 , SO 2 and OH; Z 1 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate; and n is an integer 1 to 5; wherein the chelating agent is a compound of Formula V, Y 1 is attached to L at R 11 of L 1 group , and the L is further optionally attached to one to three additional L groups, or the L is attached between the Y 3 and L 1 groups of Y 1 , or one L is attached at R 11 of L 1 group and another L is attached between the Y 3 and L 1 groups of Y 1 , and each one of the L is further optionally attached to one to three additional L groups; and wherein the chelating agent is DFO, the point of attachment of L is at the amine and wherein the * indicates the point of attachment. [00146] In some embodiments, Q is Q1, , and the compound of Formula IV has the following structure: or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 4 , R 5 , Z 1 , Z 2, S 1 and n are as defined for Formula IV.

[00147] In some embodiments, Q is Q2, , and the compound of Formula IV has the following structure: or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 6 , Z 1 , Z 2 , S 1 and n are as defined for Formula IV. [00148] In some embodiments, Q is Q3, , and the compound of Formula IV has the following structure:

or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 6 , Z 1 , Z 2 , S 1 and n are as defined for Formula IV. [00149] In some embodiments, Q is Q4, , and the compound of Formula IV has the following structure: or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 6 , Z 1 , Z 2 , S 1 and n are as defined for Formula IV. [00150] In some embodiments, Q is Q5, , and the compound of Formula IV has the following structure: or a salt and/or solvate thereof, wherein Y 1 , Y 2 , R 3 , R 6 , Z 1 , S 1 and n are as defined for Formula IV.

[00151] In some embodiments, when Q is (Q1), (Q2), (Q3) or (Q4), the stereochemistry at the carbon to which Z 2 is bonded is either R or S. In some embodiments, the stereochemistry at the carbon to which Z 2 is attached is R. In some embodiments, the stereochemistry at the carbon to which Z 2 is attached is S. [00152] In some embodiments, R 4 and R 5 are independently selected from C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl. In some embodiments, R 4 and R 5 are independently selected from C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl. In some embodiments, R 4 and R 5 are independently selected from CH 2 CH 2 CH 3 , C(CH 3 ) 3 , CH(CH 3 )CH 2 CH 3 and CH 2 CH(CH 3 ) 2 , CH(CH 3 ) 2 , CH 2 CH 3 and CH 3 . In some embodiments, R 4 and R 5 are independently selected from CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 and CH 3 . In some embodiments, at least one of R 4 and R 5 is CH 3 . In some embodiments, each one of R 4 and R 5 is CH 3 . [00153] In some embodiments, R 6 is H. [00154] In some embodiments, Z 2 is selected from C 1-10 alkylene, C 2-10 alkenylene and C 2-10 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2- 6 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is selected from C 1-4 alkylene, C 2-4 alkenylene and C 2- 4 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is C4alkylene. In some embodiments, Z 2 is C1alkylene. [00155] In some embodiments, Z 1 is selected from C 1-10 alkylene, C 2-10 alkenylene and C 2-10 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2- 6alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is selected from C 1-4 alkylene, C 2-4 alkenylene and C 2- 4 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is C 3 alkylene. [00156] In some embodiments, R 3 is sulfonate. [00157] In some embodiments, L is selected from

[00158] In some embodiments, L is [00159] The ZW linker is a permanent zwitterionic group which possesses both a positive and a negative charge simultaneously. In some embodiments, the permanent zwitterionic group is formed at physiological pH of 5.5-7.5. [00160] In some embodiments, the ZW linker is a natural or unnatural amino acid with a primary amine. In some embodiments, the natural amino acid is lysine. In some embodiments, the unnatural amino acid is pyridyl-alanine. [00161] In some embodiments, Y 1 is a complex comprising a chelating agent and one or more radionuclides, wherein the chelating agent is DFO. [00162] In some embodiments, Y 1 is a complex comprising a chelating agent and one or more radionuclides, wherein the chelating agent is a compound of Formula V: [00163] In some embodiments, when the chelating agent is a compound of Formula V, R 7 , R 8 , R 9 and R 10 are independently selected from H and C 1-3 alkyl. In some embodiments, R 7 , R 8 , R 9 and R 10 are independently selected from H and C 1-2 alkyl. In some embodiments, at least one of R 7 , R 8 , R 9 and R 10 is C 1-2 alkyl. In some embodiments, R 7 is CH 3 . In some embodiments, each one of R 8 , R 9 and R 10 is H. [00164] In some embodiments, each a, c and e is an integer independently selected from 4, 5 and 6. In some embodiments, a, c and e are different. In some embodiments, a, c and e are 5. [00165] In some embodiments, each b and d is an integer independently selected from 1, 2 and 3. In some embodiments, b and d are different. In some embodiments, b and d are 2. [00166] In some embodiments, f is selected from the integer 1, 2 and 3. In some embodiments, f is 2. [00167] In some embodiments, when Y is R 12 is selected from H and C 1- 2alkyl. In some embodiments, R 12 is selected from H and CH 3 . In some embodiments, R 12 is CH 3 . [00168] In some embodiments, when Y is R 13 , R 14 , R 15 and R 16 are independently selected from H and C 1-3 alkyl. In some embodiments, R 13 , R 14 , R 15 and R 16 are independently selected from H and C 1-2 alkyl. In some embodiments, at least one of R 13 , R 14 , R 15 and R 16 is C 1-2 alkyl. In some embodiments, R 16 is CH 3 . In some embodiments, each one of R 13 , R 14 and R 15 is H. [00169] In some embodiments, each g, l and k is an integer independently selected from 4, 5 and 6. In some embodiments, g, l and k are different. In some embodiments, g, l and k are 5. [00170] In some embodiments, each h and j is an integer independently selected from 1, 2 and 3. In some embodiments, h and j are different. In some embodiments, h and j are 2. [00171] In some embodiments, a, c and e are 5 and b and d are 2 and the compound of Formula V has the following structure: (V), wherein R 7 , R 8 , R 9 , R 10 , L 1 and Y 3 are as defined above. [00172] In some embodiments, when Y 3 is , g, i and k are 5 and h and j are 2 and the compound of Formula V has the following structure: (V). [00173] In some embodiments, the compound of Formula V is selected from DFO 2 K;

DFO-Km;

p-SCN-Ph-DFOKm. [00174] In some embodiments, n is an integer 1 to 3. In some embodiments, n is an integer 1. In some embodiments, n is an integer 2. As such, the conjugate of the present application comprises at least one ZW linker. In some embodiments, the conjugate of the present application comprises two ZW linkers. [00175] In some embodiments, the chelating agent is a compound of Formula V and Y 1 is attached to L at R 11 of L 1 group . In some embodiments, the L is further optionally attached to one or two additional L groups. In some embodiments, the L is further optionally attached to one L group. [00176] In some embodiments, the chelating agent is a compound of Formula V and L is attached between the Y 3 and L 1 groups of Y 1 . In some embodiments, L is further optionally attached to one or two additional L groups. [00177] In some embodiments, the chelating agent is a compound of Formula V and one L is attached at R 11 of L 1 group , and another L is attached between the Y 3 and L 1 groups of Y 1 . In some embodiments, L group attached at R 11 of L 1 group is further attached to one to three additional L groups. In some embodiments, L group attached between the Y 3 and L 1 groups of Y 1 is further attached to one additional L group. [00178] In some embodiments, when the chelating agent is DFO, the point of attachment of L is at the amine . [00179] In some embodiments, Y 1 -L is selected from DFO- I-(R)-PZ3;

[00180] In some embodiments, S 1 is a biomolecule conjugating group selected from NH 2 , OH, SH, N 3 , CO 2 H, ONH 2 , NHNH 2 , C(O)C 1-4 alkyl, C≡CH, SCN, C(O)NH 2 , NHC(X)NH 2 , C 1-4 alkyleneN 3 , NHC(O)C 1-4 alkylene N 3 , NHC(O)C 1-4 alkyleneONH 2 , NHC(O)C 1-4 alkyleneNHNH 2 , NHC(O)OC 1-4 alkyleneN 3 , C(O)NHC 1-4 alkylene-phenylene- tetrazine, and , wherein represents a single or a double bond and X is O, S or NH. A person skilled in the art would understand that other functional groups known in the art can also be used as a biomolecule conjugating group. This includes any functional group comprising, for example, a nucleophilic group, an electrophilic group, a Michael acceptor, a group that participates in a Click reaction, a group that participates in a cross-coupling reaction, a group that is activated to participate in a nucleophilic displacement reaction, and the like. [00181] In some embodiments, the biomolecule conjugating group is , wherein X is O, S or NH. [00182] In some embodiments, the biomolecule conjugating group is . [00183] In some embodiments, the radionuclide is selected from a transition metal, rare-earth metal, lanthanide, actinide and metalloid. [00184] Radionucleotides that can be used in the present application include but are not limited to the following elements and their isotopes: 225 Ac, 226 Ac, 227 Ac, 228 Ac, 105 Ag, 106m Ag, 110m Ag, 111 Ag, 112 Ag, 113 Ag, 239 Am, 240 Am, 242 Am, 244 Am, 37 Ar, 71 As, 72 As, 73 As, 74 As 76 As, 77 As, 209 At, 210 At, 191 Au, 192 Au, 193 Au, 194 Au, 195 Au, 196 Au, 196m2 Au, 198 Au, 198m Au, 199 Au 200m Au, 128 Ba, 131 Ba, 133m Ba, 135m Ba, 140 Ba, 7 Be, 203 Bi, 204 Bi, 205 Bi, 206 Bi, 210 Bi, 212 Bi, 243 Bk, 244 Bk 245 Bk, 246 Bk, 248m Bk, 250 Bk, 76 Br, 77 Br, 80m Br, 82 Br, 11 C, 14 C, 45 Ca, 47 Ca, 107 Cd, 115 Cd, 115 mCd 117m Cd, 132 Ce, 133m Ce, 134 Ce, 135 Ce, 137 Ce, 137m Ce, 139 Ce, 141 Ce, 143 Ce, 144 Ce, 246 Cf, 247 Cf, 253 Cf, 254 Cf, 240 Cm, 241 Cm, 242 Cm, 252 Cm, 55 Co, 56 Co, 57 Co, 58 Co, 58m Co, 60 Co, 48 Cr, 51 Cr, 127 Cs, 129 Cs 131 Cs, 132 Cs, 136 Cs, 137 Cs, 61 Cu, 62 Cu, 64 Cu, 67 Cu, 153 Dy, 155 Dy, 157 Dy, 159 Dy, 165 Dy, 166 Dy, 160 Er 161 Er, 165 Er, 169 Er, 171 Er, 172 Er, 250 Es, 251 Es, 253 Es, 254 Es, 254m Es, 255 Es, 256m Es, 145 Eu, 146 Eu, 147 Eu 148 Eu, 149 Eu, 150m Eu, 152m Eu, 156 Eu, 157 Eu, [ 18 F]AIF, 52 Fe, 59 Fe, 251 Fm, 252 Fm, 253 Fm, 254 Fm, 255 Fm, 257 Fm 66 Ga, 67 Ga, 68 Ga, 72 Ga, 73 Ga, 146 Gd, 147 Gd, 149 Gd, 151 Gd, 153 Gd, 159 Gd, 68 Ge, 69 Ge, 71 Ge, 77 Ge 170 Hf, 171 Hf, 173 Hf, 175 Hf, 179m2 Hf, 180m Hf, 181 Hf, 184 Hf, 192 Hg, 193 Hg, 193m Hg, 195 Hg, 195m Hg, 197 Hg 197m Hg, 203 Hg, 160m Ho, 166 Ho, 167 Ho, 123 l, 124 l, 126 l, 130 l, 132 l, 133 l, 135 l, 109 ln, 110 ln, 111 ln, 114m ln 115m ln, 184 lr, 185 lr, 186 lr, 187 lr, 188 lr, 189 lr, 190 lr, 190m2 lr, 192 lr, 193m lr, 194 lr, 194m2 lr, 195m lr, 42 K, 43 K, 76 Kr 79 Kr, 81m Kr, 85m Kr, 132 La, 133 La, 135 La, 140 La, 141 La, 262 Lr, 169 Lu, 170 Lu, 171 Lu, 172 Lu, 174m Lu, 176m Lu 177 Lu, 177m Lu, 179 Lu, 257 Md, 258 Md, 260 Md, 28 Mg, 52 Mn, 90 Mo, 93m Mo, 99 Mo, 100 Mo, 13 N, 24 Na, 90 Nb, 91m Nb 92m Nb, 95 Nb, 95m Nb, 96 Nb, 138 Nd, 139m Nd, 140 Nd, 147 Nd, 56 Ni, 57 Ni, 66 Ni, 234 Np, 236 Np, 99 Mo, Np, 238 Np 239 Np, 15 0, 182 0s, 183 0s, 183m Os, 185 0s, 189m Os, 191 0s, 191m Os, 193 0s, 32 P, 33 P, 228 Pa, 229 Pa, 230 Pa, 232 Pa, 233 Pa, 234 Pa, 200 Pb, 201 Pb, 202 mPb, 203 Pb, 209 Pb, 212 Pb, 100 Pd, 101 Pd, 103 Pd, 109 Pd 111m Pd, 112 Pd, 143 Pm, 148 Pm, 148m Pm, 149 Pm, 151 Pm, 204 Po, 206 Po, 207 Po, 210 Po, 139 Pr, 142 Pr, 143 Pr, 145 Pr, 188 Pt, 189 Pt, 191 Pt, 193m Pt, 195m Pt, 197 Pt, 200 Pt, 202 Pt, 234 Pu, 237 Pu, 243 Pu, 245 Pu, 246 Pu, 247 Pu 223 Ra, 224 Ra, 225 Ra, 81 Rb, 82 Rb, 82 mRb, 83 Rb, 84 Rb, 86 Rb, 181 Re, 182 Re, 182m Re, 183 Re, 184 Re, 184m Re, 186 Re, 188 Re, 189 Re, 190m Re, 99 Rh, 99m Rh, 100 Rh, 101m Rh, 102 Rh, 103m Rh, 105 Rh, 211 Rn, 222 Rn, 97 Ru, 103 Ru, 105 Ru, 35 S, 118m Sb, 119 Sb, 120 Sb, 120m Sb, 122 Sb, 124 Sb, 126 Sb, 127 Sb, 128 Sb, 129 Sb, 43 Sc, 44 Sc, 44m Sc, 46 Sc, 47 Sc, 48 Sc, 72 Se, 73 Se, 75 Se, 153 Sm, 156 Sm, 110 Sn, 113 Sn, 117m Sn, 119m Sn, 121 Sn, 123 Sn, 125 Sn, 82 Sr, 83 Sr, 85 Sr, 89 Sr, 91 Sr, 173 Ta, 175 Ta, 176 Ta, 177 Ta, 180 Ta, 182 Ta 183 Ta, 184 Ta, 149 Tb, 150 Tb, 151 Tb, 152 Tb, 153 Tb, 154 Tb, 154m Tb, 154m2 Tb, 155 Tb, 156 Tb, 156m Tb 156m2 Tb, 160 Tb, 161 Tb, 94 Tc, 95 Tc, 95m Tc, 96 Tc, 97m Tc, 99m Tc, 118 Te, 119 Te, 119m Te, 121 Te, 121m Te, 123m Te, 125m Te, 127 Te, 127m Te, 129m Te, 131m Te, 132 Te, 227 Th, 229 Th, 231 Th, 234 Th, 45 Ti, 198 TI, 199 TI, 200 TI, 201 TI, 202 TI, 204 TI, 165 Tm, 166 Tm, 167 Tm, 168 Tm, 170 Tm, 172 Tm, 173 Tm, 230 U, 231 U, 237 U, 240 U, 48 V, 178 W, 181 W, 185 W, 187 W, 188 W, 122 Xe, 125 Xe, 127 Xe, 129m Xe, 131m Xe, 133 Xe, 133m Xe, 135 Xe, 85m Y, 86 Y, 87 Y, 87m Y, 88 Y, 90 Y, 90m Y, 91 Y, 92 Y, 93 Y, 166 Yb, 169 Yb, 175 Yb, 62 Zn, 65 Zn, 69m Zn, 71m Zn, 72 Zn, 86 Zr, 88 Zr, 89 Zr, 95 Zr, and 97 Zr. The skilled person would understand that any other radionuclide known in the art can also be used in the conjugate of the present application. [00185] In some embodiments, the targeting ligand is a receptor specific moiety. In some embodiments, the targeting ligand is selective of specific for a cell surface molecule expressed on the surface of a target cell. In some embodiments, the targeting ligand is selective or specific for the targeted organ or tissue. In some embodiments, the targeting ligand of the present application directing the conjugate of the present application to a targeted tissue, organ, receptor or other biologically expressed composition. [00186] Examples of targeting ligands include, without limiting, proteins, peptides and peptidomimetics such as arginine-glycine-aspartic acid (RGD)-containing peptides and peptidomimetics, amino-acid sequences, antibodies or fragments thereof such as Fab fragments and antigen binding sites of antibodies, single-chain variable fragments of antibodies, nucleotide sequences, DNA sequences, RNA sequences, peptide nucleic acid (PNA) sequences, carbohydrates, and steroids. In some embodiments, the targeting ligand is selected from an oligonucleotide, an oligopeptide, a protein, a peptide and a small molecule compound. [00187] Examples of targeting ligands include, without limiting, gemtuzumab, inotuumab, trastuzumab (Herceptin), HD37, M195, LMB2, lym1, 8106, HMFG1, CC49, rituximab, epratuzumab, lorvotuzumab, 2C 3 , imgn388, SAR3419, BilB062, brentixumab, glembatumumab, SGN-75, PSMA ADC, ASG-5ME or mdx-1203. In some embodiments, the targeting antibody is a variant of gemtuzumab, inotuumab, trastuzumab (Herceptin), HD37, M195, LMB2, lym1, 8106, HMFG1, CC49, rituximab, epratuzumab, lorvotuzumab, 2C 3 , imgn388, SAR3419, BilB062, brentixumab, glembatumumab, SGN-75, PSMA ADC, ASG-5ME, mdx-1203, TATE, TOC, PSMA, bombesin derivatives (e.g. RM2, BBN and the like), FAPI derivatives, and the like. A person skilled in the art would understand that any other targeting ligands known in the art can also be used in the conjugate of the present application. [00188] The present application further includes a conjugate of Formula VI, or a salt and/or solvate thereof: wherein Y 1 is a complex comprising a chelating agent, wherein the chelating agent is desferrioxamine (DFO) or a compound of the following formula; wherein R 7 , R 8 , R 9 and R 10 are independently selected from H and C 1-4 alkyl; each a, c and e is an integer independently selected from 3, 4, 5, 6 and 7; each b and d is an integer independently selected from 1, 2, 3 and 4; L 1 is a linker group ; Y 3 is or ; R 11 is selected from C 1-10 alkyl and C 1-6 alkylenephenyl, optionally substituted by one of NH 2 , OH, SH, N 3 , CO 2 H and , wherein X is O, S or NH; R 12 , R 13 , R 14 , R 15 and R 16 are independently selected from H and C 1-4 alkyl; f is an integer selected from 1, 2, 3 and 4; each g, l and k is an integer independently selected from 3, 4, 5, 6 and 7; each h and j is an integer independently selected from 1, 2, 3 and 4; L is a zwitterionic (ZW) compound of the formula (VII) wherein Q is selected from Q1, Q2, Q3, Q4 and Q5:

Z 2 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 4 and R 5 are independently selected from C 1-10 alkyl, C 2-10 alkenyl and C 2-10 alkynyl; R 6 is selected from H, halo, NO 2 , SO 2 and OH; Z 1 is selected from C 1-15 alkylene, C 2-15 alkenylene and C 2-15 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, NH and S; R 3 is an anion containing group selected from sulfonate, carboxylate, sulfate and phosphate; R 17 is absent or selected from H or OH; and n is an integer 1 to 5; provided that wherein the chelating agent is a compound of Formula V, Y 1 is attached to L at R 11 of L 1 group , then R 17 is H and the L is further optionally attached to one to three additional L groups, or the L is attached between the Y 3 and L 1 groups of Y 1 and then R 17 is absent, or one L is attached at R 11 of L 1 group and another L is attached between the Y 3 and L 1 groups of Y 1 , and each one of the L is further optionally attached to one to three additional L groups; and wherein the chelating agent is DFO, the point of attachment of L is at the amine and then R 17 is H, and wherein the * indicates the point of attachment. [00189] In some embodiments, Q is Q1, , and the compound of Formula VI has the following structure: or a salt and/or solvate thereof, wherein Y 1 , R 3 , R 4 , R 5 , Z 1 , Z 2 and n are as defined for Formula VI.

[00190] In some embodiments, Q is Q2, , and the compound of Formula VI has the following structure: or a salt and/or solvate thereof, wherein Y 1 , R 3 , R 6 , Z 1 , Z 2 , and n are as defined for Formula VI. [00191] In some embodiments, Q is Q3, , and the compound of Formula VI has the following structure:

or a salt and/or solvate thereof, wherein Y 1 , R 3 , R 6 , Z 1 , Z 2 and n are as defined for Formula VI. [00192] In some embodiments, Q is Q4, , and the compound of Formula VI has the following structure: or a salt and/or solvate thereof, wherein Y 1 , R 3 , R 6 , Z 1 , Z 2 and n are as defined for Formula VI. [00193] In some embodiments, Q is Q5, , and the compound of Formula VI has the following structure: or a salt and/or solvate thereof, wherein Y 1 , R 3 , R 6 , Z 1 and n are as defined for Formula VI.

[00194] In some embodiments, when Q is (Q1), (Q2), (Q3) or (Q4), the stereochemistry at the carbon to which Z 2 is bonded is either R or S. In some embodiments, the stereochemistry at the carbon to which Z 2 is attached is R. In some embodiments, the stereochemistry at the carbon to which Z 2 is attached is S. [00195] In some embodiments, R 4 and R 5 are independently selected from C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl. In some embodiments, R 4 and R 5 are independently selected from C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl. In some embodiments, R 4 and R 5 are independently selected from CH 2 CH 2 CH 3 , C(CH 3 ) 3 , CH(CH 3 )CH 2 CH 3 and CH 2 CH(CH 3 ) 2 , CH(CH 3 ) 2 , CH 2 CH 3 and CH 3 . In some embodiments, R 4 and R 5 are independently selected from CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 3 and CH 3 . In some embodiments, at least one of R 4 and R 5 is CH 3 . In some embodiments, each one of R 4 and R 5 is CH 3 . [00196] In some embodiments, R 6 is H. [00197] In some embodiments, Z 2 is selected from C 1-10 alkylene, C 2-10 alkenylene and C 2-10 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2- 6 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is selected from C 1-4 alkylene, C 2-4 alkenylene and C 2- 4 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 2 is C4alkylene. In some embodiments, Z 2 is C1alkylene. [00198] In some embodiments, Z 1 is selected from C 1-10 alkylene, C 2-10 alkenylene and C 2-10 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2- 6alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is selected from C 1-4 alkylene, C 2-4 alkenylene and C 2- 4 alkynelene, unsubstituted or substituted with one or more of halo or OH and/or are optionally interrupted by one to three heteromoieties independently selected from O, N and S. In some embodiments, Z 1 is C 3 alkylene. [00199] In some embodiments, R 3 is sulfonate. [00200] In some embodiments, L is selected from , ,

[00201] In some embodiments, L is or . [00202] The ZW linker is a permanent zwitterionic group which possesses both a positive and a negative charge simultaneously. In some embodiments, the permanent zwitterionic group is formed at physiological pH of 5.5-7.5. [00203] In some embodiments, the ZW linker is a natural or unnatural amino acid with a primary amine. In some embodiments, the natural amino acid is lysine. In some embodiments, the unnatural amino acid is pyridyl-alanine. [00204] In some embodiments, Y 1 is a complex comprising a chelating agent, wherein the chelating agent is DFO. [00205] In some embodiments, Y 1 is a complex comprising a chelating agent, wherein the chelating agent is a compound of Formula V: [00206] In some embodiments, when the chelating agent is a compound of Formula V, R 7 , R 8 , R 9 and R 10 are independently selected from H and C 1-3 alkyl. In some embodiments, R 7 , R 8 , R 9 and R 10 are independently selected from H and C 1-2 alkyl. In some embodiments, at least one of R 7 , R 8 , R 9 and R 10 is C 1-2 alkyl. In some embodiments, R 7 is CH 3 . In some embodiments, each one of R 8 , R 9 and R 10 is H. [00207] In some embodiments, each a, c and e is an integer independently selected from 4, 5 and 6. In some embodiments, a, c and e are different. In some embodiments, a, c and e are 5. [00208] In some embodiments, each b and d is an integer independently selected from 1, 2 and 3. In some embodiments, b and d are different. In some embodiments, b and d are 2. [00209] In some embodiments, f is selected from the integer 1, 2 and 3. In some embodiments, f is 2. [00210] In some embodiments, when Y is , R 12 is selected from H and C 1- 2alkyl. In some embodiments, R 12 is selected from H and CH 3 . In some embodiments, R 12 is CH 3 . [00211] In some embodiments, when Y is , R 13 , R 14 , R 15 and R 16 are independently selected from H and C 1-3 alkyl. In some embodiments, R 13 , R 14 , R 15 and R 16 are independently selected from H and C 1-2 alkyl. In some embodiments, at least one of R 13 , R 14 , R 15 and R 16 is C 1-2 alkyl. In some embodiments, R 16 is CH 3 . In some embodiments, each one of R 13 , R 14 and R 15 is H. [00212] In some embodiments, each g, l and k is an integer independently selected from 4, 5 and 6. In some embodiments, g, l and k are different. In some embodiments, g, l and k are 5. [00213] In some embodiments, each h and j is an integer independently selected from 1, 2 and 3. In some embodiments, h and j are different. In some embodiments, h and j are 2. [00214] In some embodiments, a, c and e are 5 and b and d are 2 and the compound of Formula V has the following structure: (V), wherein R 7 , R 8 , R 9 , R 10 , L 1 and Y 3 are as defined above. [00215] In some embodiments, when Y 3 is , g, i and k are 5 and h and j are 2 and the compound of Formula V has the following structure: (V). [00216] In some embodiments, the compound of Formula V is selected from DFO 2 K;

[00217] In some embodiments, n is an integer 1 to 3. In some embodiments, n is an integer 1. In some embodiments, n is an integer 2. As such, the conjugate of the present application comprises at least one ZW linker. In some embodiments, the conjugate of the present application comprises two ZW linkers. [00218] In some embodiments, the chelating agent is a compound of Formula V and Y 1 is attached to L at R 11 of L 1 group and then R 17 is H. In some embodiments, the L is further optionally attached to one or two additional L groups. In some embodiments, the L is further optionally attached to one L group. [00219] In some embodiments, the chelating agent is a compound of Formula V and L is attached between the Y 3 and L 1 groups of Y 1 and then R 17 is absent. In some embodiments, L is further optionally attached to one or two additional L groups. [00220] In some embodiments, the chelating agent is a compound of Formula V and one L is attached at R 11 of L 1 group , and another L is attached between the Y 3 and L 1 groups of Y 1 . In some embodiments, L group attached at R 11 of L 1 group is further attached to one to three additional L groups. In some embodiments, L group attached between the Y 3 and L 1 groups of Y 1 is further attached to one additional L group. [00221] In some embodiments, when the chelating agent is DFO, the point of attachment of L is at the amine and then R 17 is H . [00222] In some embodiments, the Y 1 -L is selected from DFO- I(2)-(R)-PZ3;

[00223] In some embodiments, the conjugate of Formula VI is further attached to a biomolecule conjugating group selected from NH 2 , OH, SH, N 3 , CO 2 H, ONH 2 , NHNH 2 , C(O)C 1-4 alkyl, C≡CH, SCN, C(O)NH 2 , NHC(X)NH 2 , C 1-4 alkyleneN 3 , NHC(O)C 1- 4 alkyleneN 3 , NHC(O)C 1-4 alkyleneONH 2 , NHC(O)C 1-4 alkyleneNHNH 2 , NHC(O)OC 1- 4 alkyleneN 3 , C(O)NHC 1-4 alkylene-phenylene-tetrazine, and wherein represents a single or a double bond and X is O, S or NH. A person skilled in the art would understand that other functional groups known in the art can also be used as a biomolecule conjugating group. This includes any functional group comprising, for example, a nucleophilic group, an electrophilic group, a Michael acceptor, a group that participates in a Click reaction, a group that participates in a cross- coupling reaction, a group that is activated to participate in a nucleophilic displacement reaction, and the like. [00224] In some embodiments, the chelating agent further comprises one or more radionuclides selected from a transition metal, rare-earth metal, lanthanide, actinide and metalloid. [00225] Radionucleotides that can be used in the present application include but are not limited to the following elements and their isotopes: 225 Ac, 226 Ac, 227 Ac, 228 Ac, 105 Ag, 1 06m Ag, 110m Ag, 111 Ag, 112 Ag, 113 Ag, 239 Am, 240 Am, 242 Am, 244 Am, 37 Ar, 71 As, 72 As, 73 As, 74 As 7 6 As, 77 As, 209 At, 210 At, 191 Au, 192 Au, 193 Au, 194 Au, 195 Au, 196 Au, 196m2 Au, 198 Au, 198m Au, 199 Au 2 00m Au, 128 Ba, 131 Ba, 133m Ba, 135m Ba, 140 Ba, 7 Be, 203 Bi, 204 Bi, 205 Bi, 206 Bi, 210 Bi, 212 Bi, 243 Bk, 2 44 Bk 245 Bk, 246 Bk, 248m Bk, 250 Bk, 76 Br, 77 Br, 80m Br, 82 Br, 11 C, 14 C, 45 Ca, 47 Ca, 107 Cd, 115 Cd, 1 15 mCd 117m Cd, 132 Ce, 133m Ce, 134 Ce, 135 Ce, 137 Ce, 137m Ce, 139 Ce, 141 Ce, 143 Ce, 144 Ce, 2 46 Cf, 247 Cf, 253 Cf, 254 Cf, 240 Cm, 241 Cm, 242 Cm, 252 Cm, 55 Co, 56 Co, 57 Co, 58 Co, 58m Co, 60 Co, 4 8 Cr, 51 Cr, 127 Cs, 129 Cs 131 Cs, 132 Cs, 136 Cs, 137 Cs, 61 Cu, 62 Cu, 64 Cu, 67 Cu, 153 Dy, 155 Dy, 1 57 Dy, 159 Dy, 165 Dy, 166 Dy, 160 Er 161 Er, 165 Er, 169 Er, 171 Er, 172 Er, 250 Es, 251 Es, 253 Es, 254 Es, 2 54m Es, 255 Es, 256m Es, 145 Eu, 146 Eu, 147 Eu 148 Eu, 149 Eu, 150m Eu, 152m Eu, 156 Eu, 157 Eu, [ 18 F]AIF, 52 Fe, 59 Fe, 251 Fm, 252 Fm, 253 Fm, 254 Fm, 255 Fm, 257 Fm 66 Ga, 67 Ga, 68 Ga, 72 Ga, 7 3 Ga, 146 Gd, 147 Gd, 149 Gd, 151 Gd, 153 Gd, 159 Gd, 68 Ge, 69 Ge, 71 Ge, 77 Ge 170 Hf, 171 Hf, 173 Hf, 1 75 Hf, 179m2 Hf, 180m Hf, 181 Hf, 184 Hf, 192 Hg, 193 Hg, 193m Hg, 195 Hg, 195m Hg, 197 Hg 197m Hg, 203 Hg, 1 60m Ho, 166 Ho, 167 Ho, 123 l, 124 l, 126 l, 130 l, 132 l, 133 l, 135 l, 109 ln, 110 ln, 111 ln, 114m ln 115m ln, 184 lr, 185 lr, 1 86 lr, 187 lr, 188 lr, 189 lr, 190 lr, 190m2 lr, 192 lr, 193m lr, 194 lr, 194m2 lr, 195m lr, 42 K, 43 K, 76 Kr 79 Kr, 81m Kr, 85m Kr, 132 La, 133 La, 135 La, 140 La, 141 La, 262 Lr, 169 Lu, 170 Lu, 171 Lu, 172 Lu, 174m Lu, 176m Lu 177 Lu, 177m Lu, 179 Lu, 257 Md, 258 Md, 260 Md, 28 Mg, 52 Mn, 90 Mo, 93m Mo, 99 Mo, 100 Mo, 13 N, 24 Na, 90 Nb, 91m Nb 92m Nb, 95 Nb, 95m Nb, 96 Nb, 138 Nd, 139m Nd, 140 Nd, 147 Nd, 56 Ni, 57 Ni, 66 Ni, 234 Np, 236 Np, 99 Mo, Np, 238 Np 239 Np, 15 0, 182 0s, 183 0s, 183m Os, 185 0s, 189m Os, 191 0s, 191m Os, 193 0s, 32 P, 33 P, 228 Pa, 229 Pa, 230 Pa, 232 Pa, 233 Pa, 234 Pa, 200 Pb, 201 Pb, 202 mPb, 203 Pb, 209 Pb, 212 Pb, 100 Pd, 101 Pd, 103 Pd, 109 Pd 111m Pd, 112 Pd, 143 Pm, 148 Pm, 148m Pm, 149 Pm, 151 Pm, 204 Po, 206 Po, 207 Po, 210 Po, 139 Pr, 142 Pr, 143 Pr, 145 Pr, 188 Pt, 189 Pt, 191 Pt, 193m Pt, 195m Pt, 197 Pt, 200 Pt, 202 Pt, 234 Pu, 237 Pu, 243 Pu, 245 Pu, 246 Pu, 247 Pu 223 Ra, 224 Ra, 225 Ra, 81 Rb, 82 Rb, 82 mRb, 83 Rb, 84 Rb, 86 Rb, 181 Re, 182 Re, 182m Re, 183 Re, 184 Re, 184m Re, 186 Re, 188 Re, 189 Re, 190m Re, 99 Rh, 99m Rh, 100 Rh, 101m Rh, 102 Rh, 103m Rh, 105 Rh, 211 Rn, 222 Rn, 97 Ru, 103 Ru, 105 Ru, 35 S, 118m Sb, 119 Sb, 120 Sb, 120m Sb, 122 Sb, 124 Sb, 126 Sb, 127 Sb, 128 Sb, 129 Sb, 43 Sc, 44 Sc, 44m Sc, 46 Sc, 47 Sc, 48 Sc, 72 Se, 73 Se, 75 Se, 153 Sm, 156 Sm, 110 Sn, 113 Sn, 117m Sn, 119m Sn, 121 Sn, 123 Sn, 125 Sn, 82 Sr, 83 Sr, 85 Sr, 89 Sr, 91 Sr, 173 Ta, 175 Ta, 176 Ta, 177 Ta, 180 Ta, 182 Ta 183 Ta, 184 Ta, 149 Tb, 150 Tb, 151 Tb, 152 Tb, 153 Tb, 154 Tb, 154m Tb, 154m2 Tb, 155 Tb, 156 Tb, 156m Tb 156m2 Tb, 160 Tb, 161 Tb, 94 Tc, 95 Tc, 95m Tc, 96 Tc, 97m Tc, 99m Tc, 118 Te, 119 Te, 119m Te, 121 Te, 121m Te, 123m Te, 125m Te, 127 Te, 127m Te, 129m Te, 131m Te, 132 Te, 227 Th, 229 Th, 231 Th, 234 Th, 45 Ti, 198 TI, 199 TI, 200 TI, 201 TI, 202 TI, 204 TI, 165 Tm, 166 Tm, 167 Tm, 168 Tm, 170 Tm, 172 Tm, 173 Tm, 230 U, 231 U, 237 U, 240 U, 48 V, 178 W, 181 W, 185 W, 187 W, 188 W, 122 Xe, 125 Xe, 127 Xe, 129m Xe, 131m Xe, 133 Xe, 133m Xe, 135 Xe, 85m Y, 86 Y, 87 Y, 87m Y, 88 Y, 90 Y, 90m Y, 91 Y, 92 Y, 93 Y, 166 Yb, 169 Yb, 175 Yb, 62 Zn, 65 Zn, 69m Zn, 71m Zn, 72 Zn, 86 Zr, 88 Zr, 89 Zr, 95 Zr, and 97 Zr. The skilled person would understand that any other radionuclide known in the art can also be used in the conjugate of the present application. [00226] In some embodiments, the biomolecule conjugating group is further attached to a targeting ligand. [00227] In some embodiments, the targeting ligand is a receptor specific moiety. In some embodiments, the targeting ligand is selective of specific for a cell surface molecule expressed on the surface of a target cell. In some embodiments, the targeting ligand is selective or specific for the targeted organ or tissue. In some embodiments, the targeting ligand of the present application directing the conjugate of the present application to a targeted tissue, organ, receptor or other biologically expressed composition. [00228] Examples of targeting ligands include, without limiting, proteins, peptides and peptidomimetics such as arginine-glycine-aspartic acid (RGD)-containing peptides and peptidomimetics, amino-acid sequences, antibodies or fragments thereof such as Fab fragments and antigen binding sites of antibodies, single-chain variable fragments of antibodies, nucleotide sequences, DNA sequences, RNA sequences, peptide nucleic acid (PNA) sequences, carbohydrates, and steroids. In some embodiments, the targeting ligand is selected from an oligonucleotide, an oligopeptide, a protein, a peptide and a small molecule compound. [00229] Examples of targeting ligands include, without limiting, gemtuzumab, inotuumab, trastuzumab (Herceptin), HD37, M195, LMB2, lym1, 8106, HMFG1, CC49, rituximab, epratuzumab, lorvotuzumab, 2C 3 , imgn388, SAR3419, BilB062, brentixumab, glembatumumab, SGN-75, PSMA ADC, ASG-5ME or mdx-1203. In some embodiments, the targeting antibody is a variant of gemtuzumab, inotuumab, trastuzumab (Herceptin), HD37, M195, LMB2, lym1, 8106, HMFG1, CC49, rituximab, epratuzumab, lorvotuzumab, 2C 3 , imgn388, SAR3419, BilB062, brentixumab, glembatumumab, SGN-75, PSMA ADC, ASG-5ME, mdx-1203, TATE, TOC, PSMA, bombesin derivatives (e.g. RM2, BBN and the like), FAPI derivatives, and the like. A person skilled in the art would understand that any other targeting ligands known in the art can also be used in the conjugate of the present application. [00230] In some embodiments, the salt and/or solvate of the compound and/or the conjugate of the application is a pharmaceutically acceptable salt and/or solvate. In some embodiments the pharmaceutically acceptable salt is an acid addition salt or a base addition salt. The selection of a suitable salt may be made by a person skilled in the art (see, for example, S. M. Berge, et aI., "Pharmaceutical Salts," J. Pharm. Sci.1977, 66, 1- 19). [00231] An acid addition salt suitable for, or compatible with, the treatment of subjects is any non-toxic organic or inorganic acid addition salt of any basic compound. Basic compounds that form an acid addition salt include, for example, compounds comprising an amine group. Illustrative inorganic acids which form suitable salts include hydrochloric, hydrobromic, sulfuric, nitric and phosphoric acids, as well as acidic metal salts such as sodium monohydrogen orthophosphate and potassium hydrogen sulfate. Illustrative organic acids which form suitable salts include mono-, di- and tricarboxylic acids. Illustrative of such organic acids are, for example, acetic, trifluoroacetic, propionic, glycolic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, malic, tartaric, citric, ascorbic, maleic, hydroxymaleic, benzoic, hydroxybenzoic, phenylacetic, cinnamic, mandelic, salicylic, 2-phenoxybenzoic, p-toluenesulfonic acid and other sulfonic acids such as methanesulfonic acid, ethanesulfonic acid and 2-hydroxyethanesulfonic acid. In an embodiment, the mono- or di-acid salts are formed, and such salts exist in either a hydrated, solvated or substantially anhydrous form. In general, acid addition salts are more soluble in water and various hydrophilic organic solvents, and generally demonstrate higher melting points in comparison to their free base forms. The selection criteria for the appropriate salt will be known to one skilled in the art. Other non- pharmaceutically acceptable salts such as but not limited to oxalates may be used, for example in the isolation of compounds of the application for laboratory use, or for subsequent conversion to a pharmaceutically acceptable acid addition salt. [00232] A base addition salt suitable for, or compatible with, the treatment of subjects is any non-toxic organic or inorganic base addition salt of any acidic compound. Acidic compounds that form a basic addition salt include, for example, compounds comprising a carboxylic acid group. Illustrative inorganic bases which form suitable salts include lithium, sodium, potassium, calcium, magnesium or barium hydroxide as well as ammonia. Illustrative organic bases which form suitable salts include aliphatic, alicyclic or aromatic organic amines such as isopropylamine, methylamine, trimethylamine, picoline, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2- diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, and the like. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. The selection of the appropriate salt may be useful, for example, so that an ester functionality, if any, elsewhere in a compound is not hydrolyzed. The selection criteria for the appropriate salt will be known to one skilled in the art. [00233] Solvates of the compound and/or the conjugate of the application include, for example, those made with solvents that are pharmaceutically acceptable. Examples of such solvents include water (resulting solvate is called a hydrate) and ethanol and the like. Suitable solvents are physiologically tolerable at the dosage administered. [00234] In some embodiments of the present application, the compounds described herein may have at least one asymmetric center. Where compounds possess more than one asymmetric center, they may exist as diastereomers. It is to be understood that all such isomers and mixtures thereof in any proportion are encompassed within the scope of the present application. It is to be further understood that while the stereochemistry of the compounds may be as shown in any given compound listed herein, such compounds may also contain certain amounts (for example, less than 20%, suitably less than 10%, more suitably less than 5%) of compounds of the present application having an alternate stereochemistry. It is intended that any optical isomers, as separated, pure or partially purified optical isomers or racemic mixtures thereof are included within the scope of the present application. [00235] The compounds of the present application may also exist in different tautomeric forms and it is intended that any tautomeric forms which the compounds form, as well as mixtures thereof, are included within the scope of the present application. [00236] The compounds of the present application may further exist in varying polymorphic forms and it is contemplated that any polymorphs, or mixtures thereof, which form are included within the scope of the present application. [00237] The present application also includes a composition comprising one or more conjugates of the application and a carrier. In some embodiments, the composition is a pharmaceutical composition. Therefore, the present application also includes a pharmaceutical composition comprising one or more conjugates of the application and a pharmaceutically acceptable carrier. [00238] In some embodiments, the composition of the application is for medical diagnosis, therefore the present application also includes a diagnostic composition comprising one or more conjugates of the application and a carrier. In some embodiments, when the medical diagnosis is performed in vitro, the carrier needs not be pharmaceutically acceptable. Thus, if the medical diagnosis comprises administering the diagnostic composition to a subject then the carrier is a pharmaceutically acceptable carrier. [00239] In some embodiments, the composition of the application is for theranostic applications, therefore the present application also includes a theranostic composition comprising one or more conjugates of the application and a pharmaceutically acceptable carrier. [00240] In some embodiment, the conjugate of the present application comprises at least one ZW linker. [00241] In some embodiments, the conjugate of the present application comprises two ZW linkers. [00242] In some embodiments, the ZW linker is a natural or unnatural amino acid with a primary amine. In some embodiments, the natural amino acid is lysine. In some embodiments, the unnatural amino acid is pyridyl-alanine. [00243] In some embodiments, the conjugate of the present application is a radiopharmaceutical. In some embodiments, the radiopharmaceutical is a protein-based radiopharmaceutical. In some embodiments, the radiopharmaceutical is a peptide-based radiopharmaceutical. [00244] In some embodiments, the composition of the application is for medical diagnosis. In some embodiments, the composition of the application is for radionuclide therapy. In some embodiments, the composition of the application is for theranostic applications. [00245] In some embodiments, the pharmaceutical acceptable carrier is a solvent or solution. In some embodiments, the pharmaceutical compositions comprise, for example, one or more of water, buffers (for example, neutral buffered saline, phosphate buffered saline, citrates and/or acetates), ethanol, oil, carbohydrates (for example, glucose, fructose, mannose, sucrose and/or mannitol), proteins, polypeptides and/or amino acids such as glycine, antioxidants (e.g. sodium bisulfite), tonicity adjusting agents (such as potassium and calcium chloride), chelating agents such as EDTA and/or glutathione, vitamins and/or preservatives. [00246] The compounds and/or conjugates of the application are administered to a subject in a variety of forms depending on the selected route of administration, as will be understood by those skilled in the art. For example, a compound and/or conjugate of the application is administered by oral, inhalation, parenteral, buccal, sublingual, nasal, rectal, vaginal, patch, pump, minipump, topical or transdermal administration and the pharmaceutical compositions formulated accordingly. Conventional procedures and ingredients for the selection and preparation of suitable compositions are described, for example, in Remington’s Pharmaceutical Sciences (2000 - 20th edition) and in The United States Pharmacopeia: The National Formulary (USP 24 NF19) published in 1999. [00247] In some embodiments, the pharmaceutical composition is formulated for parenteral administration, including subcutaneous, intradermal, intravascular (for example, intravenous), intramuscular, spinal, intracranial, intrathecal, intraocular, periocular, intraorbital, intrasynovial or intraperitoneal injection, as well as any similar injection or infusion technique. Parenteral administration may be by continuous infusion over a selected period of time. [00248] In some embodiments, a compound and/or conjugate of the application is orally administered, for example, with an inert diluent or with an assimilable edible carrier, or it is enclosed in hard or soft shell gelatin capsules, or it is compressed into tablets, or it is incorporated directly with the food of the diet. In some embodiments, the compound and/or conjugate is incorporated with excipient and used in the form of ingestible tablets, buccal tablets, troches, capsules, caplets, pellets, granules, lozenges, chewing gum, powders, syrups, elixirs, wafers, aqueous solutions and suspensions, and the like. In the case of tablets, carriers that are used include lactose, corn starch, sodium citrate and salts of phosphoric acid. Pharmaceutically acceptable excipients include binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystalline cellulose or calcium phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulphate). In embodiments, the tablets are coated by methods well known in the art. In the case of tablets, capsules, caplets, pellets or granules for oral administration, pH sensitive enteric coatings, such as Eudragits™ designed to control the release of active ingredients are optionally used. Oral dosage forms also include modified release, for example immediate release and timed- release, formulations. Examples of modified-release formulations include, for example, sustained-release (SR), extended-release (ER, XR, or XL), time-release or timed-release, controlled-release (CR), or continuous-release (CR or Contin), employed, for example, in the form of a coated tablet, an osmotic delivery device, a coated capsule, a microencapsulated microsphere, an agglomerated particle, e.g., as of molecular sieving type particles, or, a fine hollow permeable fiber bundle, or chopped hollow permeable fibers, agglomerated or held in a fibrous packet. Timed-release compositions are formulated, for example as liposomes or those wherein the active compound is protected with differentially degradable coatings, such as by microencapsulation, multiple coatings, etc. Liposome delivery systems include, for example, small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. In some embodiments, liposomes are formed from a variety of phospholipids, such as cholesterol, stearylamine or phosphatidylcholines. For oral administration in a capsule form, useful carriers or diluents include lactose and dried corn starch. [00249] In some embodiments, liquid preparations for oral administration take the form of, for example, solutions, syrups or suspensions, or they are suitably presented as a dry product for constitution with water or other suitable vehicle before use. When aqueous suspensions and/or emulsions are administered orally, the compound of the application is suitably suspended or dissolved in an oily phase that is combined with emulsifying and/or suspending agents. If desired, certain sweetening and/or flavoring and/or coloring agents are added. Such liquid preparations for oral administration are prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, methyl cellulose or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters or ethyl alcohol); and preservatives (e.g., methyl or propyl p-hydroxybenzoates or sorbic acid). Useful diluents include lactose and high molecular weight polyethylene glycols. [00250] It is also possible to freeze-dry the compounds and/or conjugates of the application and use the lyophilizates obtained, for example, for the preparation of products for injection. [00251] In some embodiments, the compound and/or the conjugate of the application is administered parenterally and for example, solutions of a compound and/or conjugate of the application are prepared in water suitably mixed with a surfactant such as hydroxypropylcellulose. In some embodiments, dispersions are prepared in glycerol, liquid polyethylene glycols, DMSO and mixtures thereof with or without alcohol, and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. For parenteral administration, sterile solutions of the compounds and/or conjugates of the application are usually prepared, and the pH’s of the solutions are suitably adjusted and buffered. For intravenous use, the total concentration of solutes should be controlled to render the preparation isotonic. For ocular administration, ointments or droppable liquids are delivered, for example, by ocular delivery systems known to the art such as applicators or eye droppers. In some embodiment, such compositions include mucomimetics such as hyaluronic acid, chondroitin sulfate, hydroxypropyl methylcellulose or polyvinyl alcohol, preservatives such as sorbic acid, EDTA or benzyl chromium chloride, and the usual quantities of diluents or carriers. For pulmonary administration, diluents or carriers will be selected to be appropriate to allow the formation of an aerosol. [00252] In some embodiments, the compound and/or the conjugate of the application is formulated for parenteral administration by injection, including using conventional catheterization techniques or infusion. Formulations for injection are, for example, presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. In some embodiments, the compositions take such forms as sterile suspensions, solutions or emulsions in oily or aqueous vehicles, and contain formulating agents such as suspending, stabilizing and/or dispersing agents. In all cases, the form is sterile and is fluid to the extent that easy syringability exists. Alternatively, the compounds and/or conjugates of the application are suitably in a sterile powder form for reconstitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. [00253] In some embodiments, compositions for nasal administration are conveniently formulated as aerosols, drops, gels and powders. For intranasal administration or administration by inhalation, the compounds and/or conjugates of the application are conveniently delivered in the form of a solution, dry powder formulation or suspension from a pump spray container that is squeezed or pumped by the subject or as an aerosol spray presentation from a pressurized container or a nebulizer. Aerosol formulations typically comprise a solution or fine suspension of the compound and/or conjugate in a physiologically acceptable aqueous or non-aqueous solvent and are usually presented in single or multidose quantities in sterile form in a sealed container, which, for example, take the form of a cartridge or refill for use with an atomising device. Alternatively, the sealed container is a unitary dispensing device such as a single dose nasal inhaler or an aerosol dispenser fitted with a metering valve which is intended for disposal after use. Where the dosage form comprises an aerosol dispenser, it will contain a propellant which is, for example, a compressed gas such as compressed air or an organic propellant such as fluorochlorohydrocarbon. Suitable propellants include but are not limited to dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, heptafluoroalkanes, carbon dioxide or another suitable gas. In the case of a pressurized aerosol, the dosage unit is suitably determined by providing a valve to deliver a metered amount. In some embodiments, the pressurized container or nebulizer contains a solution or suspension of the active compound. Capsules and cartridges (made, for example, from gelatin) for use in an inhaler or insufflator are, for example, formulated containing a powder mix of a compound of the application and a suitable powder base such as lactose or starch. The aerosol dosage forms can also take the form of a pump-atomizer. [00254] Compositions suitable for buccal or sublingual administration include tablets, lozenges, and pastilles, wherein a compound and/or conjugate of the application is formulated with a carrier such as sugar, acacia, tragacanth, or gelatin and glycerine. Compositions for rectal administration are conveniently in the form of suppositories containing a conventional suppository base such as cocoa butter. [00255] Suppository forms of the compounds and/or conjugates of the application are useful for vaginal, urethral and rectal administrations. Such suppositories will generally be constructed of a mixture of substances that is solid at room temperature but melts at body temperature. The substances commonly used to create such vehicles include but are not limited to theobroma oil (also known as cocoa butter), glycerinated gelatin, other glycerides, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weights and fatty acid esters of polyethylene glycol. See, for example: Remington's Pharmaceutical Sciences, 16th Ed., Mack Publishing, Easton, PA, 1980, pp. 1530-1533 for further discussion of suppository dosage forms. [00256] In some embodiments a compound and/or conjugate of the application is coupled with soluble polymers as targetable drug carriers. Such polymers include, for example, polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide- phenol, polyhydroxy-ethylaspartamide-phenol, or polyethyleneoxide-polylysine substituted with palmitoyl residues. Furthermore, in some embodiments, a compound and/or conjugate of the application is coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates and crosslinked or amphipathic block copolymers of hydrogels. [00257] In some embodiments, compounds and/or conjugates of the application may be coupled with viral, non-viral or other vectors. Viral vectors may include retrovirus, lentivirus, adenovirus, herpesvirus, poxvirus, alphavirus, vaccinia virus or adeno- associated viruses. Non-viral vectors may include nanoparticles, cationic lipids, cationic polymers, metallic nanoparticles, nanorods, liposomes, micelles, microbubbles, cell- penetrating peptides, or lipospheres. Nanoparticles may include silica, lipid, carbohydrate, or other pharmaceutically acceptable polymers. [00258] A compound and/or conjugate of the application including pharmaceutically acceptable salts and/or solvates thereof is suitably used on their own but will generally be administered in the form of a pharmaceutical composition in which the one or more compounds and/or conjugates of the application (the active ingredient) is in association with a pharmaceutically acceptable carrier. Depending on the mode of administration, the pharmaceutical composition will comprise from about 0.05 wt% to about 99 wt% or about 0.10 wt% to about 70 wt%, of the active ingredient, and from about 1 wt% to about 99.95 wt% or about 30 wt% to about 99.90 wt% of a pharmaceutically acceptable carrier, all percentages by weight being based on the total composition. [00259] The present application also includes kits. Any of the components disclosed herein may be combined in the form of a kit. In some embodiments, the kit comprises one or more compounds of the application, one or more conjugates of the application and/or one or more compositions of the application. In some embodiments, the kit further comprises instructions for use in a method or use of the application. [00260] In some embodiments, the kit comprises a container or package and a label or package insert on or associated with the container. In some embodiments, the container or package will include at least one bottle, vial, syringe, blister pack and/or other container. The containers may be formed from a variety of materials such as glass or plastic. In some the containers hold a composition of the application which comprises an amount of one or more compounds and/or conjugates of the application that are effective for treating and/or imaging a condition. In some embodiments, the containers have a sterile access port (for example the containers may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). In some embodiments, the label or package insert indicates that the compound, conjugate and/or composition of the application is used for treating and/or imaging a condition of choice. Diagnostic and/or Therapeutic Methods and Uses of the Application [00261] The present application includes a method of diagnosing and/or monitoring one or more diseases, disorders or conditions comprising administering an effective amount of one or more conjugates of the application to a subject in need thereof and performing a medical diagnostic method on the subject. [00262] The present application also includes a use of one or more conjugates of the application in a medical diagnostic method or a use of one or more conjugates of the application for preparation of a composition for use in a medical diagnostic method. [00263] In some embodiments, the medical diagnostic method is performed using single photon emission computed tomography (SPECT, nuclear), positron emission tomography (PET, nuclear), magnetic resonance imaging (MRI, non-nuclear), optical imaging (visible and near-infrared dyes – non-nuclear) or a combination thereof. Examples of combinations of multiple modalities are PET/CT, PET/optical/CT, PET/MRI and the like. Methods of performing such imaging techniques are well known to those skilled in the art. [00264] In some embodiments, the medical diagnostic method is a peptide-targeted imaging. [00265] The present application also includes a method of treatment of one or more diseases, disorders or conditions, comprising administering an effective amount of one or more conjugates of the application to a subject in need thereof. [00266] The present application also includes a use of one or more conjugates of the application for treatment of one or more diseases, disorders or conditions or a use of one or more conjugates of the application for preparation of a medicament for treatment of one or more diseases, disorders or conditions. [00267] The present application also includes a method of radionuclide therapy comprising administering an effective amount of one or more conjugates of the application to a subject in need thereof. [00268] The present application also includes a use of one or more conjugates of the application for radionuclide therapy or a use of one or more conjugates of the application for preparation of a medicament for radionuclide therapy. [00269] In some embodiments, the radionuclide therapy is a peptide-receptor radionuclide-therapy (PRRT). [00270] The present application also includes a method of theranostic treatment comprising administering an effective amount of one or more conjugates of the application to a subject in need thereof and performing a medical diagnostic method and radionuclide therapy on the subject. [00271] In some embodiments, the treatment and/or diagnostic methods are for one or more diseases, disorders or conditions associated with cellular proliferation. In some embodiments, conditions that are treated and/or diagnosed are various cancers, thyroid diseases (e.g., hyperthyroidism or thyrotoxicosis), blood disorders (e.g., Polycythemia vera, an excess of red blood cells produced in the bone marrow), and/or cellular proliferation in blood vessels following balloon angioplasty and/or stent placement (known as restenosis). [00272] In some embodiments, the cellular proliferation is due to a cancer. [00273] In some embodiments, the cancer is adrenal cancer, bladder cancer, blood cancer, bone cancer, brain cancer, breast cancer, carcinoma, cervical cancer, colon cancer, colorectal cancer, corpus uterine cancer, ear, nose and throat (ENT) cancer, endometrial cancer, esophageal cancer, gastrointestinal cancer, head and neck cancer, Hodgkin's disease cancer, intestinal cancer, kidney cancer, larynx cancer, leukemia, liver cancer, lymph node cancer, lymphoma, lung cancer, melanoma, mesothelioma, myeloma, nasopharynx cancer, neuroblastoma, non-Hodgkin's lymphoma, oral cancer, ovarian cancer, pancreatic cancer, penile cancer, pharynx cancer, prostate cancer, rectal cancer, sarcomcancer, seminomcancer, skin cancer, stomach cancer, teratomcancer, testicular cancer, thyroid cancer, uterine cancer, vaginal cancer, vascular tumor cancer, and/or cancer from metastases thereof. [00274] Treatment methods comprise administering to a subject a therapeutically effective amount of one or more of the conjugates of the application and optionally consist of a single administration, or alternatively comprise a series of administrations, and optionally comprise concurrent administration or use of one or more other therapeutic agents. For example, in some embodiments, the conjugates of the application are administered at least once a week. In some embodiments, the conjugates are administered to the subject from about one time per two or three weeks, or about one time per week to about once daily for a given treatment. In another embodiment, the conjugates are administered 2, 3, 4, 5 or 6 times daily. The length of the treatment period depends on a variety of factors, such as the severity of the disease, disorder or condition, the age of the subject, the concentration and/or the activity of the conjugates of the application, and/or a combination thereof. It will also be appreciated that the effective dosage of the conjugate used for the treatment may increase or decrease over the course of a particular treatment regime. Changes in dosage may result and become apparent by standard diagnostic assays known in the art. In some instances, chronic administration may be required. For example, the conjugates are administered to the subject in an amount and for duration sufficient to treat the subject. In some embodiments treatment comprise prophylactic treatment. For example, a subject with early cancer can be treated to prevent progression, or alternatively a subject in remission can be treated with a conjugate of the application to prevent recurrence. [00275] The dosage of conjugates of the application varies depending on many factors such as the pharmacodynamic properties of the conjugates, the mode of administration, the age, health and weight of the recipient, the nature and extent of the symptoms, the frequency of the treatment and the type of concurrent treatment, if any, and the clearance rate of the conjugate in the subject to be treated. One of skill in the art can determine the appropriate dosage based on the above factors. Conjugates of the application may be administered initially in a suitable dosage that may be adjusted as required, depending on the clinical response. Dosages will generally be selected to maintain a serum level of conjugates of the application from about 0.01 µg/cc to about 1000 µg/cc, or about 0.1 µg/cc to about 100 µg/cc. As a representative example, oral dosages of one or more conjugates of the application will range between about 0.01 mg per day to about 1000 mg per day for an adult, suitably about 0.1 mg per day to about 500 mg per day, more suitably about 1 mg per day to about 200 mg per day. For parenteral administration, a representative amount is from about 0.001 mg/kg to about 10 mg/kg, about 0.01 mg/kg to about 10 mg/kg, about 0.01 mg/kg to about 1 mg/kg or about 0.1 mg/kg to about 1 mg/kg will be administered. For oral administration, a representative amount is from about 0.001 mg/kg to about 10 mg/kg, about 0.1 mg/kg to about 10 mg/kg, about 0.01 mg/kg to about 1 mg/kg or about 0.1 mg/kg to about 1 mg/kg. For administration in suppository form, a representative amount is from about 0.1 mg/kg to about 10 mg/kg or about 0.1 mg/kg to about 1 mg/kg. Conjugates of the application may be administered in a single daily, weekly or monthly dose or the total daily dose may be divided into two, three or four daily doses. [00276] In some embodiments, when administering one or more conjugates of the application the total dose of absorbed radiation may include about 3 grays (Gy) to about 20 Gy, about 2 Gy to about 10 Gy, about 1 Gy to about 10 Gy, about 1 Gy, about 5 Gy, about 10 Gy, about 25 Gy, about 50 Gy, about 75 Gy, about 100 Gy, about 200 Gy, about 300 Gy, about 400 Gy, about 500 Gy, about 600 Gy, about 700 Gy, about 800 Gy, about 900 Gy or about 1000 Gy. [00277] In some embodiments doses of absorbed radiation are achieved by delivering an appropriate amount of one or more conjugates of the application. Exemplary amounts of conjugates include about 0.05 mg/kg to about 5.0 mg/kg administered to a subject per day in one or more doses. For certain indications, in some embodiments, the total daily dose is about 0.05 mg/kg to about 3.0 mg/kg administered intravenously to a subject one to three times a day, including administration of total daily doses of about 0.05 mg/kg/day to about 3.0 mg/kg/day, about 0.1 mg/kg/day to about 3.0 mg/kg/day, about 0.5 mg/kg/day to about 3.0 mg/kg/day, about 1.0 mg/kg/day to about 3.0 mg/kg/day, about 1.5 mg/kg/day to about 3.0 mg/kg/day, about 2.0 mg/kg/day to about 3.0 mg/kg/day, about 2.5 mg/kg/day to about 3.0 mg/kg/day or about 0.5 mg/kg/day to about 3.0 mg/kg/day of one or more conjugates of the application using 60-minute QD, BI D, or TI D intravenous infusion dosing. In some embodiments, additional doses range from about 0.1 μg/kg to about 5 μg/kg or from about 0.5 μg/kg to about 1 μg/kg. In some embodiments, a dose is about 1 μg/kg, about 20 μg/kg, about 40 μg/kg, about 60 μg/kg, about 80 μg/kg, about 100 μg/kg, about 200 μg/kg, about 350 μg/kg, about 500 μg/kg, about 700 μg/kg, about 0.1 mg/kg to 5 about mg/kg, or from about 0.5 μg/kg to about 1 mg/kg. In some embodiments, a dose is about 1 mg/kg, about 10 mg/kg, about 20 mg/kg, about 40 mg/kg, about 60 mg/kg, about 80 mg/kg, about 100 mg/kg, about 200 mg/kg, about 400 mg/kg, about 500 mg/kg, about 700 mg/kg, about 750 mg/kg, about 1000 mg/kg, or more. [00278] In some embodiments, therapeutically effective amounts of radionuclides are achieved by administering single or multiple doses during the course of an imaging and/or treatment regimen (e.g. , daily, every other day, every 3 days, every 4 days, every 5 days, every 6 days, weekly, every 2 weeks, every 3 weeks, monthly, every 2 months, every 3 months, every 4 months, every 5 months, every 6 months, every 7 months, every 8 months, every 9 months, every 10 months, every 11 months or yearly). [00279] In some embodiments, effective amounts vary according to factors such as the disease state, age, sex and/or weight of the subject. In a further embodiment, the amount of a given conjugate that will correspond to an effective amount will vary depending upon factors, such as the given drug(s) or compound(s), the pharmaceutical formulation, the route of administration, the type of condition, disease or disorder, the identity of the subject being treated, and the like, but can nevertheless be routinely determined by one skilled in the art. [00280] In the context of cancers, in some embodiments, the therapeutic methods of treatment decrease the number of cancer cells, decrease the number of metastases, decrease tumour volume, increase life expectancy, induce chemo- or radiosensitivity in cancer cells, inhibit angiogenesis near cancer cells, inhibit cancer cell proliferation, inhibit tumour growth, prevent or reduce metastases, reduce cancer-associated pain and/or reduce relapse or re-occurrence of cancer. [00281] In the context of hyperthyroidism or thyrotoxicosis, in some embodiments, the therapeutic methods of treatment aid in the return of thyroid secreted hormones, such as T3 and/or T4, to closer to normal levels (e.g. to about 80 ng/dl to about 180 ng/dl and/or about 4.6 μg/dl to about 12 μg/dl, respectively). In the context of polycythemia vera, in some embodiments, the therapeutic methods of treatment aid in the return of red blood cell counts to closer to normal level (e.g. to about 4.7 million cells/μL to about 8.1 million cells/μL). [00282] In the context of restenosis, in some embodiments, the therapeutic methods comprise placing radionuclides in the region of a vessel where a stent is located or balloon angioplasty was performed to inhibit the narrowing of the vessel fur to proliferation of blood vessel cells. In some embodiments, treatment for restenosis is deemed effective if normal blood flow through the affected blood vessel is restored. [00283] In some embodiments, the subject in need of is a subject in need of imaging. In some embodiments, the subject in need of imaging is a subject in need of diagnosis, in need of locating a position for a therapeutic intervention, in need of assessment of the functioning of a body part, and/or in need of assessment of the presence of absence of a condition. [00284] In some embodiments, for use in diagnostic or therapeutic methods, the one or more compounds and/or conjugates are comprised in a pharmaceutical composition as described above. Preparation Methods of the Application [00285] The zwitterions of the present application can be prepared by various synthetic processes. The choice of particular structural features and/or substituents may influence the selection of one process over another. The selection of a particular process to prepare a given compound of the application is within the purview of the person of skill in the art. Some starting materials for preparing compounds of the present application are available from commercial chemical sources. Other starting materials, for example as described below, are readily prepared from available precursors using straightforward transformations that are well known in the art. [00286] In the Schemes below showing some embodiments of methods of preparation of zwitterions of the application, all variables are as defined in Formula I, unless otherwise stated. [00287] Accordingly, in some embodiments, a compound of Formula I, wherein Q is Q1 , R 1 is a protecting group, R 2 is OH, Z 1 is C 3 alkylene and R 3 is sulfonate, is prepared as shown in Scheme 1.

Scheme 1 [00288] Accordingly, protection of group R 2 with Pg 3 is followed by amine deprotection to form intermediate B, wherein Pg 3 is any suitable protecting group and Z 2 is as defined by Formula I. The intermediate B undergoes reductive amination by adding compound b in a presence of reducing agent, such as sodium cyanoborohydride to form intermediate C, wherein R 4 and R 5 are as defined by Formula I. The resulting intermediate C is reacted with 1,3-propanesultone in a presence of a base, such as potassium carbonate to form intermediate compound of formula D, in which Z 1 is C 3 alkylene and R 3 is sulfonate. The resulting intermediate D undergoes hydrogenolysis in a presence of palladium catalyst to provide the compound of Formula I. [00289] In some embodiments, a compound of Formula I, wherein Q is Q3 , R 1 is a protecting group, R 2 is OH, Z 1 is C 3 alkylene and R 3 is sulfonate, is prepared as shown in Scheme 2.

Scheme 2 [00290] Accordingly, protection of group R 2 with Pg 2 to form indeterminate compound of formula F, wherein Pg 1 and Pg 2 are any suitable protecting groups and Z 2 is as defined by Formula I, is followed by reaction with -1,3-propanesultone in a presence of a base, such as potassium carbonate to form intermediate compound of formula G, in which Z 1 is C 3 alkylene and R 3 is sulfonate. The resulting intermediate G undergoes hydrogenolysis in a presence of palladium catalyst to provide the compound of Formula I.

[00291] A person skilled in the art would appreciate that a similar reaction sequence can be used to prepared compounds Of formula I, wherein Q is Q2 or Q4 [00292] The chelating agents of Formula V of the present application can be prepared by various processes. The choice of particular structural features and/or substituents may influence the selection of one process over another. The selection of a particular process to prepare a given compound of the application is within the purview of the person of skill in the art. Some starting materials for preparing compounds of the present application are available from commercial chemical sources. Other starting materials, are readily prepared from available precursors using straightforward transformations that are well known in the art. [00293] The compounds of the application generally can be prepared according to the processes illustrated in the Schemes below. In the structural formulae shown below the variables are as defined in Formula V unless otherwise stated. [00294] Accordingly, in some embodiments, a compound of Formula V, wherein L 1 is , is prepared as shown in Scheme 3.

Scheme 3 [00295] Therefore a compound of Formula A, wherein R 11 is as defined in Formula V or a protected version thereof and Pg is a suitable protecting group, is reacted with a compound of Formula B or B', wherein R 11 -R 16 , j, h, I, j and k are as defined in Formula V, under amide bond forming conditions to form, after removal of the protecting group, a compound of Formula C or C' respectively. The compound of Formula C or C’ is then reacted with a compound of Formula D, wherein R 7 -R 10 , a, b, c, d, e and f are as defined in Formula V, under amide bond forming conditions, to provide after removal of any protecting groups if needed, the compound of Formula V, wherein L 1 is [00296] In some embodiments, a compound of Formula V, wherein L 1 is and Y 3 is , are prepared as shown in Scheme 4. Scheme 4 [00297] Therefore a compound of Formula K, wherein R 11 and f are as defined in Formula V and Pg 3 is a suitable protecting group, is reacted with a compound of Formula L, wherein R 12 is as defined in Formula V or a protected version thereof and Pg 4 is a suitable protecting group, under amide bond forming conditions followed by selective deprotection of Pg 4 , to provide a compound of Formula M. The compound of Formula M is then reacted with a compound of Formula J, wherein R 7 -R 10 , a, b, c, d, and e are as defined in Formula V, followed by removal of any protecting groups, to provide the compound of Formula V wherein L 1 is and Y 3 is . [00298] Amide bond forming conditions comprise any known method for the coupling of carboxylic acids and amines that is compatible with the intermediates and products shown in the above Schemes or that may be used to prepare a compound of the application. Known methods to prepare amides by the coupling of carboxylic acids and amines comprise use of either a coupling reagent or by prior conversion of the carboxylic acid into an activated derivative. Coupling reagents include, but are not limited to, any of the known peptide coupling reagents, such as 1-[bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU), 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDC), dicyclohexylcarbodiimide (DCC) diisopropylcarbodiimide (DIC), hexafluorophosphate benzotriazole tetramethyl uronium (HBTU), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU), O-(1H-6-chlorobenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU), benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyAOP) and propanephosphonic acid anhydride. [00299] In some embodiments, racemization of an enantiomer of a carboxylic acid occurs during amide bond formation using coupling reagents. In some embodiments, racemization is circumvented with 'racemization suppressing' additives such as the triazoles 1-hydroxy-benzotriazole (HOBt), 1-hydroxy-7-aza-benzotriazole (HOAt) and ethyl cyanohydroxyiminoacetate (Oxyma). [00300] Nucleophilic displacement reaction conditions comprise any known method for the reaction of a nucleophile to displace a leaving group to form a bond that is compatible with the intermediates and products shown in the above Schemes or that may be used to prepare a compound of the application. In some embodiments, such conditions comprise combining reactants in the presence of a base in a suitable solvent. [00301] Salts of the compounds of the application are generally formed by dissolving the neutral compound in an inert organic solvent and adding either the desired acid or base and isolating the resulting salt by either filtration or other known means. [00302] The formation of solvates of the compounds of the application will vary depending on the compound and the solvate. In general, solvates are formed by dissolving the compound in the appropriate solvent and isolating the solvate by cooling or using an antisolvent. The solvate is typically dried or azeotroped under ambient conditions. The selection of suitable conditions to form a particular solvate can be made by a person skilled in the art. Examples of suitable solvents are ethanol, water and the like. When water is the solvent, the molecule is referred to as a “hydrate”. [00303] Prodrugs of the compounds of the present application may be, for example, conventional esters formed with available hydroxy, thiol, amino or carboxyl groups. For example, available hydroxy or amino groups may be acylated using an activated acid in the presence of a base, and optionally, in inert solvent (e.g. an acid chloride in pyridine). Some common esters which have been utilized as prodrugs are phenyl esters, aliphatic (C1-C24) esters, acyloxymethyl esters, carbamates and amino acid esters. [00304] Throughout the processes described herein it is to be understood that, where appropriate, suitable protecting groups will be added to, and subsequently removed from, the various reactants and intermediates in a manner that will be readily understood by one skilled in the art. Conventional procedures for using such protecting groups as well as examples of suitable protecting groups are described, for example, in “Protective Groups in Organic Synthesis”, T.W. Green, P.G.M. Wuts, Wiley-Interscience, New York, (1999). It is also to be understood that a transformation of a group or substituent into another group or substituent by chemical manipulation can be conducted on any intermediate or final product on the synthetic path toward the final product, in which the possible type of transformation is limited only by inherent incompatibility of other functionalities carried by the molecule at that stage to the conditions or reagents employed in the transformation. Such inherent incompatibilities, and ways to circumvent them by carrying out appropriate transformations and synthetic steps in a suitable order, will be readily understood to one skilled in the art. Examples of transformations are given herein, and it is to be understood that the described transformations are not limited only to the generic groups or substituents for which the transformations are exemplified. References and descriptions of other suitable transformations are given in “Comprehensive Organic Transformations – A Guide to Functional Group Preparations” R.C. Larock, VHC Publishers, Inc. (1989). References and descriptions of other suitable reactions are described in textbooks of organic chemistry, for example, “Advanced Organic Chemistry”, March, 4th ed. McGraw Hill (1992) or, “Organic Synthesis”, Smith, McGraw Hill, (1994). Techniques for purification of intermediates and final products include, for example, straight and reversed phase chromatography on column or rotating plate, recrystallisation, distillation and liquid-liquid or solid-liquid extraction, which will be readily understood by one skilled in the art. [00305] Techniques for purification of intermediates and final products include, for example, normal and reversed phase chromatography on column (manual, automated, and HPLC) or rotating plate, recrystallisation, distillation and liquid-liquid or solid-liquid extraction, which will be readily understood by one skilled in the art. [00306] In some embodiments, a compound of the application is reacted with a complex comprising a chelating agent and one or more radionuclides under suitable conditions. In some embodiments, the complex comprising one radionuclide. In some embodiments, the complex comprising two radionuclides. In some embodiments, the compound of the application is reacted with a targeting ligand under suitable conditions. In some embodiments, the compound of the application is reacted with a biomolecule conjugating group under suitable conditions. In some embodiments, a conjugate of the application is formed using, for example, solid phase peptide synthesis under suitable conditions. [00307] In some embodiments, the biomolecule conjugating group is reacted with the targeting ligand under suitable conditions. Targeting ligand can be conjugated to the biomolecule conjugating group of the application using any known methods for reacting, for example, but not limited to, a nucleophilic group, an electrophilic group, a Michael acceptor, a group that participates in a Click reaction, a group that participates in a cross- coupling reaction, a group that is activated to participate in a nucleophilic displacement reaction, to form a covalent bond. Such reactions are described in, for example “Comprehensive Organic Transformations – A Guide to Functional Group Preparations” R.C. Larock, VHC Publishers, Inc. (1989), “Advanced Organic Chemistry”, March, 4th ed. McGraw Hill (1992) or “Organic Synthesis”, Smith, McGraw Hill, (1994). [00308] The following non-limiting examples are illustrative of the present application. EXAMPLES The following non-limiting examples are illustrative of the present application. Materials and Methods Radiochemistry [00309] Gallium-68 was procured from an in-house Eckert & Ziegler generator system (3131−0901 IGG100−30M), with a TiO 2 -based stationary phase, eluting [ 68 Ge]Ge 4+ /[ 68 Ga]Ga 3+ , 1.11 GBq (30 mCi) with HCl (0.1 M). Activity was experimentally measured using a CRC-55tR dose calibrator (Capintec, Inc., NJ, USA) [44]. The activity was concentrated following generator elution using Bond Elut SCX Cartridge, 100 mg, particle size 40 μm (Agilent, cat. no.12102013) and eluted with 500 μL of 5M NaCl and 0.05M HCl solution [45]. Reverse-phase radio-high-performance liquid chromatography (HPLC) was performed on a ThermoFisher Vanquish UHPLC (Dual λ Absorbance Detector, AcclaimPolar Advantage II, 120A, C18, 5.0 μm 4.6 x 250 mm column, Thermo Scientific) along with a flow count radiodetector F (Eckert & Ziegler, B-FC-3500 diode). The UV-detector was set at 254 and 280 nm and the solvent system was 0.1% trifluoroacetic acid (TFA) in water (A) and 0.1% TFA in acetonitrile (B) at a flow rate of 0.65 mL/min. Radio-iTLC were eluted using silica-gel impregnated glass-microfiber instant thin layer chromatography paper (iTLC-SG, iTLC-SA, Varian) using 1:1 methanol: ammonium acetate (1.0 M; pH ~ 4) as a developing solvent and measured using an Eckert & Ziegler AR2000 detector using P10 gas, with the included WinScan software. Chemical Characterization Methods [00310] 1 H and 13 C nuclear magnetic resonance (NMR) spectra were recorded on a 500 MHz Bruker Avance NMR spectrometer at 25 °C in CDCl 3 or Methanol-d4 (MeOD). 1 H and 13 C chemical shifts were referenced to the residual protons of the deuterated solvent ( δ = 7.26 and 3.31 ppm for CDCl 3 and MeOD, respectively). Coupling constants are reported to the nearest 0.5 Hz ( 1 H NMR spectroscopy) or rounded to integer values in Hz ( 13 C NMR spectroscopy). High resolution mass spectra were measured on a JEOL AccuTOF TM GCv 4G using field desorption ionization (FDI). For the isotopic pattern only, the mass peak of the isotopologue or isotope with the highest natural abundance is given. Low resolution mass spectrometry and liquid chromatography–mass spectrometry (LCMS) were performed using an Advion Expression-L system (mass range <2000 amu). HPLC purifications were performed using a Vanquish HPLC equipped with C18 reversed- phase column (Inspire Semipreparative DIKMA; 5 μm, 21.2 × 250 mm), a VF-D40-A UV detector, two VF-P10-A pumps, a Chromeleon 7 communication software, and a DIONEX UltiMate 3000 fraction collector, using a flow rate of 7 mL/ min and a gradient of CH 3 CN:H 2 O (both with 0.1% TFA). LCMS was performed by coupling the above Thermofisher Vanquish with the above Advion Expression-L system. Reagents [00311] All solvents and reagents were purchased from commercial suppliers (Sigma- Aldrich, St. Louis, MO; TCI America, Portland, OR; Fisher Scientific, Waltham, MA; AK Scientific, Union City, USA) and were used as received unless otherwise indicated. Fmoc-L-Lys(Boc)-OH that used for synthesizing Fmoc-L-Lys(ZW)-OH ≥ 98.0% (cat. no.47624); benzyl alcohol ≥ 99.0% (cat. no.402834); formaldehyde solution 37 wt. % in H 2 O (cat. no.252549) and palladium on carbon 10 wt. % loading (cat. no.205699) were purchased from Sigma-Aldrich. Fmoc-β-(3-pyridyl)-D-Ala-OH was purchased from Sigma Aldrich.1,3-propanesultone 99.92% (GC) (cat. no. 22005) was purchased from CHEM-IMPEX INT’L INC. All standard Nα-Fmoc amino acids used [Fmoc-L-Thr(tBu)-OH, Fmoc-L-Cys(Trt)-OH, Fmoc-L-Cys(Acm)-OH, Fmoc-L-Lys(Boc)-OH, Fmoc-D Trp(Boc)- OH, Fmoc-L-Tyr(tBu)-OH, and Fmoc-LPhe-OH] were purchased from AK Scientific, and coupling reagents such N,N,N′,N′-tetramethyl-O(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) and 1-[bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium3-oxide hexafluorophosphate (HATU) were purchased from Fischer Scientific. Fmoc-N-amido-PEG4-acid was purchased from BroadPharma (California, USA). Fmoc-L-Thr(tBu)-Wang Resin was purchased from New England Peptide (capacity 0.8 mmol/g).1,4,7,10-tetraazacyclododecane-1,4,7-tris (t-butyl acetate) (DO3A-tBu) was purchased from Macrocyclics, Inc. Water and buffers used for radiochemistry were millipure (18.2 mΩ) and further rendered metal-free by stirring overnight with 1.2 g Chelex-100 resin (200−400 mesh, Bio-Rad Laboratories, Inc.) per liter of solution and passing them through a 0.22 μm filter (Nalgene media filters). Example 1: Zwitterion (ZW) preparation Synthesis of Fmoc-Lys(ZW)-COOH Amino Acid [00312] The preparation of Fmoc-Lys(ZW)-COOH Amino Acid is shown in Scheme 5 and the synthetic details are provided below: Scheme 5 Synthesis of (S)-benzyl 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6- aminohexanoate ((S)-LZ1) [00313] In a 100 mL round bottom flask, Fmoc-Lys(Boc)-OH (1.0 g, 2.1 mmol) and benzyl alcohol (10 mL) were mixed and stirred at room temperature. Then SOCl 2 (328 µL, 4.50 mmol) was added in a slow dropwise manner and the whole reaction was stirred at 80 º C for three hours. Cold diethyl ether (20 mL) was added and triturated and washed with more diethyl ether (3 X 20 mL) to give (S)-LZ1 (0.97 gm; 98%) as white solid. 1 H NMR (500 MHz, MeOD) δ(ppm): 1.44-1.88 (m, 6H), 2.88 (t, 2H, J=15.8 Hz), 4.17-4.23 (m, 2H), 4.28 (q, 1H, J=17.6 Hz), 4.39 (q, 1H, J=6.7 Hz), 5.15 (q, 2H, J=16.5 Hz), 7.27-7.80 (m, 13H). 13 C NMR (MeOD) δ(ppm): 23.83, 27.97, 31.89, 40.47, 55.23, 67.93, 120.9, 126.1, 126.2, 128.1, 128.8, 129.3, 129.5, 137.2, 142.6, 145.1, 145.3, 158.7, 173.6. HRMS-ESI m/z calcd for [C28H30N2O4 + H] + :459.2278, found: 459.2287. Synthesis of (S)-benzyl 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6- (dimethylamino)hexanoate ((S)-LZ2) [00314] Each of Fmoc-Lys-OBn ((S)-LZ1) (0.970 g, 1.96 mmol), formaldehyde (1.95 mL, 19.6 mmol, 37% w/v solution in H 2 O) and acetic acid (0.337 mL, 5.88 mmol) were dissolved in 50 mL ethanol and stirred at room temperature for five minutes. Sodium cyanoborohydride (0.493 g, 7.84 mmol) was added in portions. The reaction mixture was left to stir at room temperature for four hours. The solvent was removed and the residue was purified using reverse phase chromatography (80-20% H 2 O: 20-80% CH 3 CN gradient) and lyophilized to give (S)-LZ2 as a white powder (0.620 g, 60%). 1 H NMR (500 MHz, MeOD) δ(ppm): 1.37-1.48 (m, 6H), 2.72 (s, 6H), 2.90 (t, 2H, J=15.8 Hz), 4.19-4.23 (m, 2H), 4.30 (q, 1H, J=17.6 Hz), 4.43 (q, 1H, J=6.7 Hz), 5.16 (q, 2H, J=16.5 Hz), 7.28- 7.81 (m, 13H). 13 C NMR (MeOD) δ(ppm): 21.0, 22.4, 28.9, 40.7, 52.2, 55.9, 64.9, 65.0, 117.9, 123.1, 125.2, 125.8, 126.3, 126.6, 134.2, 139.6, 142.1, 155.7, 170.7. HRMS-ESI m/z calcd for [C 3 0H34N2O4 + H] + : 487.2597, found: 487.2619. Synthesis of (S)-3-((5-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-(ben zyloxy)-6- oxohexyl)dimethyla-mmonio)propane-1-sulfonate ((S)-LZ3) [00315] 1,3-propanesultone (0.284 g, 2.33 mmol) was refluxed in acetone (10 mL) for 30 minutes. Separately, Fmoc-Lys(dimethyl)-OBn ((S)-LZ2) (0.610 g, 1.17 mmol) was stirred with potassium carbonate (0.323 g, 2.34 mmol) in acetone (5 mL) for 30 minutes at room temperature. After 30 minutes elapsed, Fmoc-Lys(dimethyl)-OBn solution was added to 1,3-propanesultone and the reaction was left for another hour to reflux and then stirred overnight at room temperature. The solvent was removed and the residue was purified by using reverse phase chromatography (80-20% H 2 O: 20-80% CH 3 CN gradient) and lyophilized to give (S)-LZ3 as a white powder (0.434 g, 40-61%). 1 H NMR (500 MHz, MeOD) δ(ppm): 1.41-1.79 (b, 6H), 2.15 (q, 2H, J=16.8 Hz), 2.85 (t, 2H, J=15.8 Hz), 3.05 (s, 6H), 3.23(q, 2H, J=15.9 Hz), 3.48 (q, 2H, J=16.8 Hz), 4.19-4.42 (m, 4H), 5.18 (q, 2H, J=17.8 Hz), 7.29-7.81 (m, 13H). 13 C NMR (MeOD) δ(ppm): 16.9, 19.9, 20.8, 28.8, 48.3, 52.2, 60.8, 62.0, 64.9, 65.0, 118.0, 123.2, 125.2, 125.3, 125.8, 126.4, 126.6, 134.2, 139.6, 142.1, 155.7, 170.6. HRMS-ESI m/z calcd for [C 3 3H40N2O7S + Na] + : 541.1984, found: 541.1983. Synthesis of (S)-3-((5-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5- carboxypentyl)dimethylammonio) propane-1-sulfonate ((S)-LZ4) [00316] Both Fmoc-Lys(ZW)-OBn ((S)-LZ3) (0.430 g, 0.706 mmol) and palladium (0.0755 g; 0.071 mmol, 10% Pd/C) were dissolved in methanol (20 mL) in a Schlenk flask that was connected to water respiratory from side neck to create vacuum and from the top neck it was attached to a balloon filled with H 2 gas. Three cycles of vacuum and purging with H 2 gas were performed then filled with H 2 gas and left the reaction to stir at room temperature for four hours. The completion of the reaction was confirmed by thin- layer chromatography (TLC) and the catalyst was removed by filtration through celite powder. The solvent was removed under vacuo and the residue was purified using reverse phase chromatography (80-20% H 2 O: 20-80% CH 3 CN gradient) and lyophilized to give (S)-LZ4 as a white powder (0.293 gm, 80%). 1 H NMR (500 MHz, MeOD) δ(ppm): 1.48-2.21 (b, 10H), 2.89 (t, 2H, J= 15.5 Hz), 3.09 (s, 6H), 3.52(q, 2H, J= 16.5 Hz), 4.19- 4.44 (m, 4H), 7.34-7.83 (m, 8H). 13 C NMR (MeOD) δ(ppm): 19.8, 22.9, 23.8, 32.1, 51.2, 55.0, 63.8, 65.0, 67.9, 120.9126.2, 126.3, 128.1, 128.2, 128.8, 142.6, 145.1, 145.3, 158.7,175.7. HRMS-ESI m/z calcd for [C26H34N2O7S + H] + : 519.2159, found: 519.2190. Synthesis of Fmoc-Ala-Pyr(ZW)-COOH Amino Acid [00317] The preparation of Fmoc-Ala-Pyr(ZW)-COOH Amino Acid is shown in Scheme 6 and the synthetic details are provided below:

Scheme 6 Synthesis of (R)-benzyl 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(pyridin-3- yl)propanoate ((R)-PZ1): [00318] In a 100 mL round bottom flask, Fmoc-Ala-Pyr-OH (1.0 g, 2.6 mmol) and Cs 2 CO 3 (0.85 g, 2.6 mmol) were stirred in 30 mL CH 3 CN at room temperature for 15 minutes. This was followed by addition of benzyl bromide (0.29 mL, 2.5 mmol), then the reaction mixture was stirred at room temperature overnight. The solvent was removed, and 30 mL H 2 O was added and extracted three times with ethyl acetate and dried over sodium sulfate. The residue was purified with normal phase chromatography (20-100% ethyl acetate: hexane gradient) to give (R)-PZ1 (0.65 g; 55%) as an off-white solid. 1 H NMR (500 MHz, DMSO-d 6 ) δ(ppm): 2.92-2.96 (dd, 1H, J= 8.11Hz), 3.10-3.14 (dd, 1H, J= 6.32 Hz), 4.13-4.26 (m, 3H), 4.34-4.39 (dd, 1H, J= 3.40 Hz), 5.12-5.13 (d, 2H, J= 5.55 Hz), 7.26-7.42 (m, 10H), 7.60-7.68 (m, 3H), 7.87 (s, 1H), 7.89(s, 1H), 8.01(s, NH), 8.42- 8.48(m, 2H). 13 C NMR (DMSO-d 6 ) δ(ppm): 33.92, 46.98, 55.54, 66.18, 66.60, 120.6, 123.7, 125.6, 127.5,128.1, 128.2, 128.5, 128.8, 133.4, 136.2, 137.1, 141.1, 144.1, 148.2, 150.7, 156.4, 171.9. HRMS-ESI m/z calcd for [C 30 H 26 N 2 O 4 + H] + : 479.20, found: 479.197 with ppm Error 1.18. Synthesis of (R)-3-(3-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(b enzyloxy)-3- oxopropyl)pyridin-1-ium-1-yl)propane-1-sulfonate ((R)-PZ2): [00319] Fmoc-Ala-Pyr-OBn ((R)-PZ1) (0.75g, 1.57 mmol) was stirred with potassium carbonate (0.65 g, 4.71 mmol) in 30 mL of CH 3 CN for 15 minutes at room temperature then the solution was filtered to a new 100 mL round bottom flask to remove all insoluble potassium carbonate behind.1,3-propanesultone (1.92 g, 15.7 mmol) was added and the reaction mixture refluxed at 100 ºC overnight. The solvent was removed, and the residue was diluted with H 2 O (30 mL), then extracted three times with 30 mL of ethyl acetate, and then dried over sodium sulfate. The crude mixture was purified using reverse phase chromatography (80-20% H 2 O: 20-80% CH 3 CN gradient) and lyophilized to give (R)-PZ2 as a white powder (0.65 g, 69%). 1 H NMR (500 MHz, DMSO-d 6 ) δ(ppm): 2.18-2.24 (m, 2H), 2.42 (t, 2H, J= 8.11 Hz), 3.10-3.15 (dd, 1H, J= 8.11 Hz), 4.17 (t, 1H, J= 6.81 Hz), 4.23-4.32 (m, 2H), 4.54-4.58 (m, 1H), 4.65 (t, 2H, J= 7.04 Hz), 5.15 (s, 2H), 7.29-7.42 (m, 10H), 7.62 (t, 2H, J= 7.97 Hz), 7.88(d, 2H, J= 7.57 Hz), 7.98-8.03 (m, 2H), 8.42(s, NH), 8.94-9.06(m, 2H). 13 C NMR (DMSO-d 6 ) δ(ppm): 27.79, 33.49, 46.98, 47.52, 54.38, 60.20, 66.18, 66.82, 120.6, 125.5, 127.5,128.1, 128.3, 128.9, 136.1, 138.8, 141.1, 144.1, 145.6, 146.2, 156.4, 171.2. HRMS-ESI m/z calcd for [C 33 H 32 N 2 O 7 S + H] + : 601.20, found: 601.2005 with ppm Error 0.332. Synthesis of (R)-3-(3-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2- carboxyethyl)pyridin-1-ium-1-yl)propane-1-sulfonate ((R)-PZ3): [00320] Both Fmoc-Ala-Pyr(ZW)-OBn ((R)-PZ2) (0.65 g, 1.08 mmol) and palladium on carbon (0.18 g; 10.8 mmol, 10% Pd/C) were dissolved in methanol (20 mL) in a Schlenk flask connected, with mild vacuum drawn using a water aspirator from the side neck, and a balloon filled with H 2 gas and fitted with a glass valve was attached to the top neck. Three cycles of vacuum and purging with H 2 gas were performed, then the reaction vessel was filled with H 2 gas and left to stir at room temperature for 2 hours. The completion of the reaction was confirmed by reversed-phase TLC and the catalyst was removed by filtration through celite powder. The solvent was removed under vacuo and the residue was purified using reverse phase chromatography (80-20% H 2 O: 20-80% CH 3 CN gradient) and lyophilized to give (R)-PZ3 as a white powder (0.44 g, 80%). 1 H NMR (500 MHz, DMSO-d 6 ) δ(ppm): 2.20-2.25 (m, 2H), 2.44 (t, 2H, J= 3.29 Hz), 3.06-3.10 (dd, 1H, J= 8.09 Hz), 4.17 (t, 1H, J= 6.87 Hz), 4.21-4.28 (m, 2H), 4.34-4.38 (m, 1H), 4.67 (t, 2H, J= 7.02 Hz), 7.31 (t, 2H, J= 7.43 Hz ), 7.40 (t, 2H, J= 7.43 Hz), 7.64(t, 2H, J= 7.94 Hz), 7.79 (d, 1H, J= 8.48 Hz), 7.88(d, 2H, J= 7.48 Hz), 8.04 (t, 1H, J= 4.67 Hz), 8.44 (d, NH), 8.96-9.05(m, 2H), 13.1 (b, OH). 13 C NMR (DMSO-d 6 ) δ(ppm): 27.80, 33.73, 46.99, 47.53, 54.44, 60.170, 66.10, 120.6, 125.6, 127.5,127.7, 128.1, 128.3, 139.3, 141.1, 143.5, 144.1, 145.5, 146.2, 156.4, 172.8. HRMS-ESI m/z calcd for [C 26 H 26 N 2 O 7 S + H] + : 511.15, found: 511.1518 with ppm Error -3.03. EXAMPLE 2: DOTA-(ZW)n-TATE Preparation Synthesis and Purification of DOTA-TATE and DOTA-(ZW)n-TATEs [00321] For the synthesis and purification of each of DOTA-TATE, DOTA-PEG4- TATE, DOTA-(ZW)1-PEG4-TATE (DOTA-(I-(S)-LZ4)1-PEG4-TATE), DOTA-(ZW) 2 -PEG4- TATE (DOTA-(I-(S)-LZ4) 2 -PEG4-TATE), and DOTA-(Pyr(ZW)-PEG4-TATE (DOTA-(I-(R)- RZ3)- PEG4-TATE) previously published ultrasonic agitation method was employed [44]. This bench-top solid phase peptide synthesis (SPPS) method began with 50 mg of Fmoc- Thr(tBu)-Wang resin (preloaded with first amino acid, loading capacity 0.8 mmol/g) was used as solid phase and was swelled in dimethylformamide (DMF) overnight before use. Amino acids were purchased or synthesized with Fmoc protecting groups on the N- terminus and a free carboxylic acid on the C-terminus. Peptides were built on solid phase in the C ^N direction with the unprotected N-terminus coupling to each new amino acid. Each amino acid was coupled with 2 mol equiv. relative to the resin using ultrasonic agitation and with variable coupling times depending on the amino acid (determined by Kaiser test). The Fmoc deprotection steps following each coupling step was performed using 20% piperidine in DMF for 3 minutes with ultrasonic agitation. After each single step of Fmoc deprotection and peptide coupling, the resin was washed thoroughly with DMF (3 x 1 mL) and dichloromethane (DCM) (3 x 1 mL), and the procedure was repeated until the desired peptide was obtained. In the same manner as standard SPPS method, the Kaiser test was used to optimize the reaction times needed for each ultrasonic-assisted coupling step, as the time required to reach near quantitative yield varies between amino acids. Cleavage and drying of the peptide were performed traditionally using 95% TFA, 2.5% DCM, and 2.5% triisopropylsilane (TIPS). Semipreparative reverse-phase (C18) high-performance liquid chromatography was carried out on a Thermofisher Vanquish HPLC system with a gradient elution of 20−100% B in A (A = 0.1% aqueous formic acid in H 2 O; B = CH 3 CN + 0.1% formic acid) for 45 min (flow rate 7 mL/ min). The desired peak was collected, and the organic solvent was removed in vacuo. The aqueous solution was frozen and lyophilized to give DOTA-TATE (Total Synthesis Time (TST) = 2.2 hrs), DOTA- PEG4-TATE (TST = 2.6 hrs), DOTA-(ZW)1-PEG4-TATE (TST = 3.3 hrs) and DOTA-(ZW) 2 - PEG4-TATE (TST = 4 hrs) with yields of 29%, 29%, 29% and 28%, respectively. Radiolabeling and Purification of DOTA-TATEs with [ 68 Ga]Ga 3+ [00322] Gallium [ 68 Ga]Ga 3+ activity was eluted from a commercial TiO 2 -based [ 68 Ge]Ge 4+ /[ 68 Ga]Ga 3+ generator (Eckert & Ziegler), according to the manufacturer’s instructions using 6 mL of 0.1 M HCl prepared from 30% HCl (TraceSELECT Ultra, Fluka) as eluent. If the desired activity (60-80 MBq) in 500 µL of abovementioned eluent was not obtained, then the concentration procedure of the activity was followed. In brief, the 6 mL of activity was passed through a preconditioned SCX column (Preconditioning: 1 mL 5.5 M HCl, 10 mL chelex treated H 2 O, and 10 mL air) and the activity released with ≤ 500 µL of 5 M NaCl and 0.05 M HCl solution. The pH was adjusted to 3.8-4 using 1.0 M ammonium acetate buffer pH = 4) and 14 nmol of the peptides were added and the reaction mixture was incubated in 95 °C on a shaker at 900 RPM for 12 minutes. The crude [ 68 Ga]Ga-DOTA-TATEs products were purified by Sep-Pak light (Waters) solid- phase extraction cartridge that was previously conditioned and equilibrated with 10 mL of deionized water, 10 mL pure ethanol and 10 mL of deionized water. The trapped labeled peptides were released in different fractions using 1 mL of EtOH:0.9% NaCl (1:2 ratio). The fraction with the highest activity was used for further in vitro and in vivo studies by taking in account that the alcohol percentage should be less than 10%. Determination of Partition Coefficient (logD 7.4 ) [00323] The lipophilicity of each one of the [ 68 Ga]Ga-DOTA-TATEs were assessed as described in the literature [46]. In brief, two phases of 1-octanol and phosphate buffer (PBS) at a pH of 7.4 were presaturated with each other. The presaturated 1-octanol (3.0 mL) was added to 3.0 mL of presaturated PBS that had about 0.3 MBq of labelled [ 68 Ga]Ga-DOTA-TATEs. The mixture was vortexed for 1.0 minute at room temperature then centrifuged for 1.0 minute at 3000 RPM. 1.0 mL of each phase was taken and measured its activity in automated gamma counter. LogD7.4 was determined for at least three experiments using Equation 1 below, where CPM (count per minute) is the reading from the gamma counter. (1) LogD7.4= log(CPMoctanol/CPMbuffer) Serum Stability In Vitro [00324] Serum stability was determined using a previously published method [47]. Aliquots of each one of the [ 68 Ga]Ga-DOTA-TATEs (5.0 MBq) were added to 0.4 mL human or mice serum and incubated at 37 °C. Aliquots (20 μL) were taken at various time intervals (10, 30, 60, 90, 120 minutes) and quenched in ice-cold acetonitrile. The samples were centrifuged, and the supernatants were diluted further with deionized water and were analyzed by radio- HPLC (a flow rate 0.65 mL/min with a gradient of CH 3 CN: H 2 O with 0.1% TFA in both).5.0 MBq of [ 68 Ga]Ga-DOTA-TATEs were prepared in 0.4 mL of PBS and used as a reference in the radio-HPLC measurement for the stability in serum study. Plasma-Protein Binding (PPB) [00325] Serum binding assay for each one of [ 68 Ga]Ga-DOTA-TATEs were carried out as described in the literature [48]. Compendiously, labelled [ 68 Ga]Ga-DOTA-TATEs (4-3 MBq) were added to freshly prepared 0.1 mL of anticoagulated human or mice plasma and the mixtures were incubated for 120 minutes at 37 ^ C. This was followed by addition of 1.0 mL ice-cold acetonitrile and centrifuged for 2 minutes at 3000 RPM. The addition of acetonitrile had been repeated two times and all supernatants (denoted as A) were combined and the total radioactivity was measured using automated gamma counter. The radioactivity of the precipitate (B) was measured as well. The plasma-protein binding rate was calculated using Equation 2 below (n=3). (2) PPB = B/(A + B)100% PET/CT and Biodistribution in Healthy and Xenograft Mice [00326] The experimental protocol was approved by the University of Saskatchewan Committee on Animal Care and procedures were performed in accordance with the guidelines of the Canadian Council on Animal Care and the Canadian Nuclear Safety Commission. Aliquots of about 200 µL of each one of [ 68 Ga]Ga-DOTA-TATEs (7-5 MBq with < 10% EtOH) were loaded to 0.5 mL syringes and > 96% Radiochemical yields (RCY) were confirmed by using radio-HPLC followed by injection to healthy CD1 female mice and xenograft bearing male NOD-SCID gamma mice (USASK colony F1005557, strain NOD .Cg-Prkdcscidll2rg) (n = 4), via tail vein catheter while in the PET scanner with image acquisition started, under anesthesia (2.5 % isoflurane in O 2 , at a flow rate of 2 mL/min). 90-minute dynamic images of all four mice were collected simultaneously on the Sofie GNEXT PET/CT small animal imaging system using the included 4-mouse heated bed. The mice were euthanized (by cervical dislocation while they were under the effect of anesthesia) at 2 hrs post injection and blood and specific organs were harvested, weighed, and residual activity in the organs were measured by using an automated gamma counter. All images were reconstructed using VivoQuant ® 2020 software (patch 1 64 bit, build vq-2020patch1-0-ga8255affc). Results and Discussion [00327] After synthesis, purification, and characterization of ZW amino acids, benchtop solid-phase peptide synthesis of DOTA-TATE and DOTA-(ZW)n-TATE derivatives (Figures 2-4 top) were performed. Then, gallium-68 radiolabeling and in vitro experiments to assess their behavior were conducted (Figure 2-4 bottom). Instant thin layer chromatography (iTLC) was used to monitor the labelling process of [ 68 Ga]Ga- DOTA-TATE (the radiochemical conversions (RCC%) based on iTLC were 97.9%), and RCC% based on radio-HPLC were more than 95% for zwitterion TATE derivatives (Table 1 below). [00328] Final apparent molar activity values for all peptide conjugates used for in vitro and in vivo studies were ~5-5.8 GBq/ μmol (135-157 mCi/ μmol). The lipophilicity of each one of the [ 68 Ga]Ga-DOTA-TATEs were assessed by octanol-water partitioning as described in the literature [Maschauer, S.; Einsiedel, J.; Haubner, R.; Hocke, C.; Ocker, M.; Hubner, H.; Kuwert, T.; Gmeiner, P.; Prante, O., Labelling and glycosylation of peptides using click chemistry: a general approach to (18)F-glycopeptides as effective imaging probes for positron emission tomography. Angew. Chem. Int. Ed. Engl.2010, 49 (5), 976-9], and there was a wide range of hydrophilicity among the tested compounds, with [ 68 Ga]Ga-DOTA-Pyr(ZW)-PEG4-TATE showing the most negative value (most polar and water soluble) at LogDPBS•7.4 = -3.57 and the standard [ 68 Ga]Ga-DOTA-TATE showing the least at LogDPBS•7.4 = -2.81, while the other compounds varied between these two values (Table 1 below). [00329] When the compounds' stability in mouse and human blood serum was examined (Figure 5-10) [Xia, Y.; Zeng, C.; Zhao, Y.; Zhang, X.; Li, Z.; Chen, Y., Comparative evaluation of (68)Ga-labeled TATEs: the impact of chelators on imaging. EJNMMI Res. 2020, 10 (1), 36], DOTA-TATE and its Lys(ZW)/Lys(ZW) 2 derivatives remained completely intact even after 2 hours , whereas the Pyr(ZW) derivative exhibited minimal ~0.4% instability in mouse serum but remained totally stable in human serum (Table 1 below). Without wishing to be limited by theory, the instability in mouse serum could be explained by the fact that murine blood serum contains more proteases than human blood serum [Puente, X. S.; Sanchez, L. M.; Overall, C. M.; Lopez-Otin, C., Human and mouse proteases: a comparative genomic approach. Nat. Rev. Genet.2003, 4 (7), 544-58]. Table 1: In vitro data results MSS = Mouse Serum Stability; HSS = Human Serum Stability; TPB = Total Protein Binding ± SD, RP-HPLC RT is the reverse-phase C18 HPLC retention time, LogD is the octanol/phosphate buffered saline (pH 7.4) partition coefficient. [00330] Experiments were performed in healthy female mice (CD1) to determine the behavior and distribution of these compounds (pharmacokinetics). Mice were catheterized via tail vein and injected while in the scanner, and dynamic PET-CT imaging was performed from time 0 until 1.5 hours post injection (n=4 each group, 4 mice in the scanner simultaneously). [00331] Rapid accumulation and prolonged retention of [ 68 Ga]Ga-DOTA-TATE in the kidneys were seen during dynamic PET/CT imaging, with late, sluggish excretion into the bladder (Figure 11, top). In contrast, [ 68 Ga]Ga-DOTA-Lys(ZW)-PEG4-TATE and [ 68 Ga]Ga-DOTA-Lys(ZW) 2 -PEG4-TATE demonstrated rapid clearance and minimal accumulation in the kidneys (Figure 11, middle and bottom, respectively). When the [ 68 Ga]Ga-DOTA-Pyr(ZW)-PEG4-TATE derivative was injected into both female and male CD1 healthy mice, a similar profile of fast clearance and minimal renal uptake was observed (Figure 12, top and bottom, respectively). After 90 minutes following injections, time-activity curve (TAC) data were extracted from dynamic PET imaging, and they were in accordance with the PET images. At the end of imaging (90 min post injection) kidney uptake values were 60.2, 3.0, 5.8 and 4.5 %ID/g for [ 68 Ga]Ga-DOTA- TATE, [ 68 Ga]Ga-DOTA-Lys(ZW)-PEG4-TATE, [ 68 Ga]Ga-DOTA-Lys(ZW) 2 -PEG4-TATE, and [ 68 Ga]Ga-DOTA-Pyr(ZW)-PEG4-TATE, respectively (Figure 13). [00332] After imaging was complete, the mice were kept awake for an additional 30 minutes before being euthanized, bringing the total period of the injection to 2 hours. Biodistribution was performed by removing and weighing individual tissues and organs, and then measuring the activity of [ 68 Ga]Ga 3+ inside each sample using an automated gamma counter. When comparing [ 68 Ga]Ga-DOTA-TATE to the three exemplary zwitterion-containing derivatives, biodistribution data revealed that the renal uptake was highest for [ 68 Ga]Ga-DOTA-TATE (~74 ± 5 ID/g%) and lowest for the zwitterion derivatives (~17-26 ± 10 ID/g%) (Figure 14). [00333] After success in healthy mice, murine xenograft models which had subcutaneous tumors over-expressing the target somatostatin receptor (SSTR2) for the TATE peptide of DOTA-TATE were tested. Each of [ 68 Ga]Ga-DOTA-TATE and its Lys(ZW) derivatives [ 68 Ga]Ga-DOTA-Lys(ZW)n-PEG4-TATE were injected into male mice (NSG) bearing AR42J (SSTR2 over-expressing) subcutaneous tumors, and they were imaged from 0-90 minutes via dynamic PET/CT imaging (Figure 15). Dynamic PET/CT imaging revealed rapid accumulation and protracted retention of [ 68 Ga]Ga-DOTA-TATE in the kidneys, with relatively slow outflow into the bladder. On the other hand, [ 68 Ga]Ga- DOTA-Lys(ZW)-PEG4-TATE showed faster clearance into the kidneys and less retention in the kidneys, which is confirmed by TAC data as well (Figure 16). The dynamic PET images and the TAC data reveal a rapid initial uptake into the kidneys between 0-5 minutes for both compounds, followed by a rapid decrease as activity was cleared into the bladder, and then a gradual increase in kidney uptake. This observation was most pronounced for the zwitterion containing compound, where less activity was retained in the kidneys than for [ 68 Ga]Ga-DOTA-TATE following the initial rapid uptake. [00334] As done for healthy mouse studies, animals were awakened for 30 minutes following PET/CT and then euthanized at 2 hours post injection. Tissue/organ samples were collected, weighed, and the amount of activity present in the samples was measured using an automated gamma counter. According to biodistribution data, renal uptake was moderate for each of [ 68 Ga]Ga-DOTA-TATE and its Lys(ZW) derivatives (31-38 %ID/g), while it was the highest for [ 68 Ga]Ga-DOTA-Lys(ZW)-PEG4-TATE in tumor and lowest in other healthy organs (Figure 17). Although the kidney uptake of ZW-containing derivatives trended lower than [ 68 Ga]Ga-DOTA-TATE, unlike in healthy mice there was not a statistically significant difference found. The ZW-containing derivatives trended lower in most healthy tissues with substantially improved profiles. Discussion [00335] The application of permanent zwitterion moieties to molecules used in vivo have shown promising performance in both NIR and nanoparticle applications. In this study, the permanent zwitterion moieties were incorporated into peptide-based radiopharmaceuticals. Synthesizing amino acids that have a sulfobetaine as side chain group and are compatible with solid phase peptide synthesis would be a modular and versatile approach. Therefore, both commercially available lysine and pyridyl alanine were modified such that they contained zwitterionic side chains and possessed standard protection chemistry for SPPS. The Fmoc-Pyr(ZW)-OH amino acid was synthesized in three steps as compared to four steps for Fmoc-Lys(ZW)-OH. Also, Fmoc-Pyr(ZW)-OH synthesis was higher yielding and more reproducible. In addition, it has a UV-active pyridine group that is advantageous when linked to a chelator or peptide or other molecular of interest that lacks a UV-active moiety. The standard DOTA-TATE (NETSPOT/LUTATHERA ® ) and ZW-containing derivatives [ 68 Ga]Ga-DOTA-Ly(ZW)- PEG4-TATE, [ 68 Ga]Ga-DOTA-Lys(ZW) 2 -PEG4-TATE, and [ 68 Ga]Ga-DOTA-Pyr(ZW)- PEG4-TATE were synthesized using manual benchtop SPPS techniques with both US and mechanical agitation, with US providing slightly higher yields and much shorter coupling times. [00336] Due to the unnatural structure and charge distribution, DOTA-TATE derivatives containing ZW amino acids were >99% stable in human and murine blood serum over 2 hours, which suggests they are not recognized by proteases in the blood. [00337] Dynamic PET/CT images in healthy female mice clearly demonstrated that the standard [ 68 Ga]Ga-DOTA-TATE had rapid accumulation and protracted retention in the kidneys with slow excretion into the bladder that started ~70 minutes post injection. However, the Lys(ZW) derivatives demonstrated rapid clearance from the kidneys, with minimal retention and faster renal elimination via bladder at ~2-5 minutes post injection. In addition, the Pyr(ZW) derivative exhibited the same profile as the Lys(ZW) derivatives in both healthy female and male mice. The ZW-containing derivatives showed a faster clearance from the kidneys into the bladder from ~0-5 minutes post injection, with a larger drop in kidney uptake and therefore less retention. At the end of dynamic PET/CT imaging (90 min p.i.) kidney uptake values were 60.2, 3.0, 5.8 and 4.5 %ID/g for [ 68 Ga]Ga-DOTA- TATE, [ 68 Ga]Ga-DOTA-Lys(ZW)-PEG4-TATE, [ 68 Ga]Ga-DOTA-Lys(ZW) 2 -PEG4-TATE, and [ 68 Ga]Ga-DOTA-Pyr(ZW)-PEG4-TATE, which for the ZW derivatives correspond to decreases of ~20-fold, ~10-fold, and ~13-fold, respectively (Figure 13). [00338] Biodistribution studies on healthy mice (both male and female) showed quantitatively that the ZW derivatives retained less activity in the kidneys than the standard [ 68 Ga]DOTA-TATE by more than 3-fold at 2 hours post injection. In addition to kidneys, the ZW derivatives exhibited a ~2-fold reduction in uptake in many healthy organs relative to the standard. In tumor-bearing mice, the biodistribution profile of all compounds changed significantly with respect to kidney uptake and healthy tissue clearance. In male mice bearing AR42J tumors the profile of the standard [ 68 Ga]Ga- DOTA-TATE was close to that of healthy female mice, with the exception of decreased retention in the kidneys and quicker elimination via bladder. While not wishing to be limited by theory, this disparity may be explained by the mice's different sexes, types, immune systems, and the presence of large SSTR2-positive tumors which can bind but will also slowly release the injected peptides (washout). It is known that radiometallated-peptides undergo a process called “washout" where they quickly accumulate in tumors via receptor binding but are also released from the tumors over time, resulting in a gradual release of tracer from the tumor and much different rates of clearance from the blood pool and healthy tissues when compared with healthy mice. While the [ 68 Ga]Ga-DOTA-Lys(ZW)- PEG4-TATE compound exhibited a profile comparable to that of healthy female mice, the kidney uptake was slightly higher presumable due to activity slowly being washed out of the tumor and back into the bloodstream. The [ 68 Ga]Ga-DOTA-Lys(ZW) 2 -PEG4-TATE compound is not represented in Figure 15 due to a malfunction in the PET/CT equipment. Even though the Lys(ZW) derivatives had average healthy tissue uptake values in tumor- bearing mice that trended ~2-3-fold lower than DOTA-TATE, the differences were not statistically significant. This is partially due to the large error values that are commonly encountered with ex vivo biodistribution experiments in mice, and from the limited sample size (n = 3-4 per group), but the differences are clear as seen in the PET/CT images, TAC data, and biodistribution values. This contrasts with experiments in healthy mice, where the ZW derivatives were statistically significantly lower in many organs with a dramatically ~3-fold lower kidney uptake. The Lys(ZW) derivative had greater tumor uptake (p = 0.058,) and lower trending uptake in most healthy organs, showing an improved biodistribution profile. In comparison to the standard, the Lys(ZW) 2 derivative showed reduced tumor uptake. While not wishing to be limited by theory, this can be explained by its rapid elimination from the blood pool, which gives it less opportunity to adhere to tumor specific receptors (Figure 17). [00339] These results demonstrate that the DOTA-TATE derivatives that are integrated with ZW modules can provide better contrast PET images due to an increase in the target-to-background ratio and could provide improved therapeutic indexes when combined with therapeutic radionuclides. Conclusions [00340] The SPPS compatible amino acids Fmoc-Lys(ZW)-OH and Fmoc-Pyr(ZW)- OH, which bear side chains with permanent zwitterions (ZW) were successfully synthesized. Using DOTA-TATE (NETSPOT/LUTATHERA ® ) as a “gold standard” radiopharmaceutical peptide, with synthesized 3 derivatives which incorporated these ZW amino acids. Peptides were successfully radiolabeled with [ 68 Ga]GaCl3 (t1/2 = 68 min) under standard conditions (12 min, 95 °C) with high radiochemical yields and purity. The ZW-containing derivatives showed higher hydrophilicity than the gold standard (more negative LogD values) and they showed high stability in both human and murine blood serum. Dynamic PET/CT of the ZW-containing derivatives in healthy mice exhibited rapid elimination and up to ~10-20-fold reduction in kidney uptake compared to substantial accumulation and lengthy retention of [ 68 Ga]Ga-DOTA-TATE. In addition, quantitative ex vivo biodistribution revealed decreases in kidney uptake for both of our ZW derivatives by more than 3-fold and by ~2-fold in other healthy organs compared to [ 68 Ga]Ga-DOTA- TATE. Interestingly, kidney uptake was not significantly decreased in male AR42J tumor bearing mice for the ZW compound [ 68 Ga]Ga-DOTA-Lys(ZW)-PEG4-TATE, but it had the highest tumor uptake (20.6 ± 2.5 %ID/g vs 13.8 ± 4.6 %ID/g) and average uptake values in the kidneys (32.9 ± 19.8 %ID/g vs 38.8 ± 42.7 %ID/g) and other healthy tissues that clearly trended lower than [ 68 Ga]Ga-DOTA-TATE and was visually impactful from PET/CT images. Also, the tumor-to-kidney ratio for [ 68 Ga] Ga-DOTA-Lys(ZW)-PEG4-TATE was 0.63. and 0.35 for the gold standard, demonstrating that the ZW-containing tracer outperforms the gold standard in terms of tumor and kidney uptake. This data suggests that amino acids bearing “permanent” zwitterions as side chain functional groups improve the biodistribution profiles of peptide-based radiopharmaceuticals. The substantially higher tumor uptake, lower kidney uptake, lower uptake in many healthy organs, resistance to proteases due to its unnatural structure and charge distribution, lack of reactivity with common bioconjugate chemistries and compatibility with standard SPPS, and high polarity with a new charge of 0 position these ZW-bearing amino acids as a valuable and highly modular approach to improving the biological distribution of peptide- based radiopharmaceuticals. Example 3: Preparation of Chelating Agents [00341] Desferrioxamine (DFO) mesylate salt was purchased from Abcam and used as received. Desferrioxamine derivative DFO 2 K Materials and Methods Materials [00342] All reagents and solvents were purchased from commercial suppliers (Sigma-Aldrich, St. Louis, MO; TCI America, Portland, OR; Fisher Scientific, Waltham, MA) and were used without further purification unless otherwise indicated. Oxyma Pure and N,N-diisopropylethylamine (DIPEA), were purchased from Sigma-Aldrich. DFO mesylate was purchased from Abcam. 1-[Bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and Boc-Lys(Z)-OH were purchased from AK Scientific. ZrCl4, EDTA, disodium salt, dihydrate (Molecular biology grade), ammonium acetate (Honeywell ≥ 99.99% trace metal basis), 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl) and potassium carbonate anhydrous were purchased from Fisher Scientific. Chemical Characterization Methods [00343] 1 H and 13 C NMR spectra were recorded on a 500 MHz Bruker Avance III HD NMR spectrometer at the Saskatchewan Structural Science Centre at the University of Saskatchewan, at 25 ºC in D 2 O, CDCl 3 or (CD 3 ) 2 SO. Chemical shifts were referenced to the residual protons of the deuterated solvents for 1 H NMR ( δ =4.79 ppm for D 2 O; δ =7.26 ppm for CDCl 3 and δ = 2.50 ppm for (CD 3 ) 2 SO. Similarly, 13 C chemical shifts were referenced to the CDCl 3 signal at 77.16 ppm and (CD 3 ) 2 SO signal at δ = 39.52 ppm. Coupling constants are reported to the nearest 0.5 Hz ( 1 H NMR spectroscopy) and for 13 C NMR spectroscopy they are rounded to integer values in Hz. Field desorption ionization (FDI) was used on JEOL AccuTOF GCv 4G mass spectrometer to measure high resolution mass spectra and only the mass peak of the isotope with the highest natural abundance is recorded for the isotopic patterns. HPLC purifications were performed on Thermofisher Vanquish HPLC using C18 reversed-phase column (Inspire Semipreparative DIKMA; 5 µm, 21.2 × 250 mm), a VF-D40-A UV detector, two VF-P10-A pumps with Chromeleon 7 communication software. A flow rate of 6-8 mL/minute was used with a gradient of MeCN:H 2 O (with 0.1% formic acid (FA) in both solvents). Low resolution mass spectrometry was performed on Advion Expression-L system (mass range <2000 amu). The Advion Expression-L was coupled with the Thermofisher Vanquish system to perform liquid chromatography–mass spectrometry (LCMS). Preparation of DFO 2 K [00344] The preparation of DFO 2 K is shown in Scheme 7 and the synthetic details are provided below:

Scheme 7 Synthesis of DFO-Lys(Z)-Boc (1) [00345] Compound 1 was prepared according to a published procedure with modification [Sarbisheh, E. K.; Salih, A. K.; Raheem, S. J.; Lewis, J. S.; Price, E. W., A High-Denticity Chelator Based on Desferrioxamine for Enhanced Coordination of Zirconium-89. Inorg. Chem. 2020, 59 (16), 11715-11727]. A solution of Boc-Lys(Z)-OH (264 mg, 0.69 mmol) in DMF (15 mL) was added to a stirring mixture of HATU (306.1 gm, 0.81 mmol) and DIPEA (0.14 mL, 0.81 mmol) in DMF (15 mL). DFO mesylate (501 mg, 0.76 mmol) was dissolved in DMF (17 mL) and DMSO (8 mL) at 65 °C. The clear solution of DFO was cooled to around 40 °C and then it was added to the above activated ester solution. The reaction was stirred at ambient temperature for 24 h and then the solvent was reduced to ~ 2 mL under reduced pressure. The residue was added dropwise to ethyl acetate and left in a spark proof -20 °C freezer for 30 minutes, to maximize precipitate formation. The precipitate was separated by centrifugation, washed with cold ethyl acetate 2 times, flash frozen in liquid nitrogen and then dried by freeze dryer. Compound 1 (632 mg, 99%) was used in the next step without further purification. 1 H NMR [(CD 3 ) 2 SO, 500 MHz]: δ 1.21 (br s, 8H, CH 2 ), 1.34 – 1.39 (m, 17H, tBu and CH 2 ), 1.96 (s, 3H, CH 3 ), 2.26 (t, J=7.3, 4H, CH 2 ), 2.57 (t, J = 7.2, 4H, CH 2 ), 2.94 – 3.01 (m, 8H, CH 2 ), 3.43 – 3.45 (m, 6H, CH 2 ), 3.80 – 3.81 (m, 1H, CH), 4.99 (s, 2H, CH 2 ), 7.23 (t, J = 5.5, 1H, NH), 7.29 – 7.37 (m, 5H, CH Ar), 7.75 (t, J = 5.4, 1H, NH), 7.79 (t, J = 5.0, 2H, NH). 13 C NMR [(CD 3 ) 2 SO, 126 MHz]: δ 20.4, 22.9, 23.4, 23.5, 26.1, 27.6, 28.1, 28.2, 28.8, 28.9, 29.1, 29.9, 31.8, 38.3, 38.4, 46.8, 47.1, 54.4, 59.8, 65.1, 77.9, 127.8, 128.4, 137.3, 155.3, 156.1, 170.2, 171.3 and 172.0. HRMS: m/z Calcd for [C44H74N8O13Na + Na] + : 945.5267; found: 945.5276. Synthesis of DFO-Lys(Z)-NH 2 (2) [00346] This Boc-deprotection procedure was modified from a published procedure [Gudmundsdottir AV, Paul CE, Nitz M. Stability studies of hydrazide and hydroxylamine- based glycoconjugates in aqueous solution. Carbohydr Res. 2009; 344: 278–84]. A mixture of trifluoroacetic acid (TFA) (0.5 mL, 6.26 mmol) and dichloromethane (DCM) (0.5 mL) was added to compound 1 (385.1 mg, 0.42 mmol). The reaction mixture was stirred for 4 hours at ambient temperature. Then the solvent was evaporated via rotary evaporator and the crude product was purified with reverse phase column chromatography (10 – 50% MeCN in water) to isolate compound 2 (327.1 mg, 95%) as a white solid. 1 H NMR [(CD 3 ) 2 SO, 500 MHz]: δ 1.21 -1.63 (m, 26H, CH 2 ), 1.96 (s, 3H, CH 3 ), 2.26 (t, J = 7.2, 4H, CH 2 ), 2.57 (t, J= 7.1, 4H, CH 2 ), 2.95 – 3.03 (m, 6H, CH 2 ), 3.05 – 3.11 (m, 2H, CH 2 ), 3.44 -3.46 (m, 7H), 5.00 (s, 2H, CH 2 ), 7.23 (t, J=5.61H, NH), 7.29 (m, 5H, CH), 7.79 (t, J=5.3, 2H, NH), 8.20 (t, J=5.3, 1H, NH), 9.65 (br s, 3H, OH). 13 C NMR [(CD 3 ) 2 SO, 126 MHz]: δ 20.4, 21.6, 23.4, 23.5, 26.0, 26.1, 27.6, 28.5, 28.9, 29.9, 30.8, 38.4, 38.7, 46.8, 52.3, 65.2, 168.3, 170.2, 171.3 and 172.0. HRMS: m/z Calcd for [C 3 9H66N8O13 + Na] + : 845.4740; found: 845.4741. Synthesis of DFO 2 -Lys-Z (3) [00347] This procedure was adapted from a published literature procedure [Figueras, E.; Martins, A.; Borbély, A.; Le Joncour, V.; Cordella, P.; Perego, R.; Modena, D.; Pagani, P.; Esposito, S.; Auciello, G.; Frese, M.; Gallinari, P.; Laakkonen, P.; Steinkühler, C.; Sewald, N. Octreotide Conjugates for Tumor Targeting and Imaging. Pharmaceutics 2019, 11 (5), 220]. DFO-COOH (470 mg, 0.71 mmol) was dissolved in a mixture of DMF (10 mL) and DMSO (4 mL) with help of heating up to 75 °C. After the solution became clear, a mixture of ethyl cyanohydroxyiminoacetate (Oxyma) (74.3 mg, 0.523 mmol) and EDC (103.3 mg, 0.665 mmol) in DMF (10 mL) was added. The mixture was stirred for 30 minutes at ambient temperature. Then a solution of 2 (391 mg, 0.48 mmol) and NaCl (27.8 mg, 0.475 mmol) in DMF (10 mL) was added, and the mixture was sonicated for 5 minutes to ensure complete dissolution. The reaction was stirred for 48 h at ambient temperature then the solvent was reduced to around 1 mL. The residue was added dropwise to ethyl acetate and left in a spark proof -20 °C freezer for 30 minutes. The precipitate was separated with help of centrifugation and washed two times with cold ethyl acetate. The crude product was purified with reverse phase chromatography (10 – 50% MeCN in water) and the product (336 mg, 32%) was collected as a white powder. 1 H NMR [(CD 3 ) 2 SO, 500 MHz]: δ 1.21 – 1.1.49 (m, 46H, CH 2 ), 1.96 (s, 3H, CH 6 ), 2.24 – 2.36 (m, 12H, CH 2 ), 2.56 – 2.28 (m, 8H, CH 2 ), 2.94 – 3.00 (m, 14H, CH 2 ), 3.43 – 3.46 (m, 12H, CH 2 ), 4.06 – 4.11 (m, 1H, CH), 4.99 (s, 2H, CH 2 ), 7.22 – 7.37 (m, 7H, CH-Ar and NH), 7.80 – 7.99 (m, 8 H, NH and OH). 13 C NMR [(CD 3 ) 2 SO, 126 MHz]: δ 20.4, 22.86, 23.5, 26.1, 27.6, 28.7, 28.8, 29.2, 29.9, 30.7, 30.8, 31.5, 38.4, 46.8, 47.1, 52.7, 65.1, 127.7, 137.3, 156.1, 170.1, 171.4, 171.6, 171.7 and 171.9. HRMS: m/z Calcd for [C68H120N16O19 + Na] + :1487.8331; found: 1487.8366. Synthesis of DFO 2 K [00348] DFO 2 K was prepared according to a published procedure with modification [Summa, V.; Petrocchi, A.; Bonelli, F.; Crescenzi, B.; Donghi, M.; Ferrara, M.; Fiore, F.; Gardelli, C.; Gonzalez Paz, O.; Hazuda, D. J.; Jones, P.; Kinzel, O.; Laufer, R.; Monteagudo, E.; Muraglia, E.; Nizi, E.; Orvieto, F.; Pace, P.; Pescatore, G.; Scarpelli, R.; Stillmock, K.; Witmer, M. V.; Rowley, M. Discovery of Raltegravir, a Potent, Selective Orally Bioavailable HIV-Integrase Inhibitor for the Treatment of HIV-AIDS Infection. J Med Chem 2008, 51 (18), 5843–5855]. In a Shlenk flask, compound 3 (47.5 mg, 30 µmol) was dissolved in ethanol (30 mL) and 10% Pd/C (6.0 mg, 5 µmol) was added. The flask was sealed with a rubber septa and connected to an H 2 gas balloon fitted with a glass stopcock and a needle, and the flask was additionally connected to vacuum via Schlenk line. The flask was put under vacuum for 15 seconds and then the vacuum was closed and the flask was purged with H 2 gas by slowly opening the glass stopcock valve. The vacuum and purging were repeated 4 times and finally the flask was left stirring under H 2 for 2 hours. After reaction completion was confirmed with low resolution mass spectrometry, the reaction mixture was filtered through celite to remove the Pd/C for safe disposal. The solvent was evaporated, and the crude product mixture was purified by semipreparative HPLC. HPLC conditions: C18 Inspire Semipreparative DIKMA; 5 µm, 21.2 × 250 mm; (20 – 30% acetonitrile in water (0.1% formic acid); flow rate, 4 mL/min, tR = 18 min). Compound DFO 2 K (39.4 mg, 90%) was obtained as an off-white solid following rotary evaporation and then freeze drying of pooled HPLC fractions. 1 H NMR [D 2 O, 500 MHz]: δ 1.24 – 1.81 (m, 44H, CH 2 ), 2.10 (s, 3H, CH 3 ), 2.44 – 2.63 (m, 12H, CH 2 ), 2.62 – 2.63 (m, 2H, CH 2 ), 2.76 (t, J=7.0, 6H, CH 2 ), 2.96 (t, J=7.7, 2H, CH 2 ), 3.12 – 3.15 (m, 12H, CH 2 ), 3.56 – 3.62 (m, 12H, CH 2 ), 4.14 – 4.17 (m, 1H, CH). 13 C NMR D 2 O, 126 MHz]: δ 19.2, 22.2, 23.0, 25.4, 26.2, 17.6, 27.9, 30.4, 30.8, 38.7, 39.1, 47.7, 47.8, 53.9, 173.5, 173.8, 174.3, 174.8, and 174.9. HRMS: m/z Calcd for [C60H110N14O19 + 2H] 2+ : 666.4109; found: 666.4123. Preparation of DFO-Km Materials and Methods Materials [00349] All reagents and solvents were purchased from commercial suppliers (Sigma-Aldrich, St. Louis, MO; TCI America, Portland, OR; Fisher Scientific, Waltham, MA) and were used without further purification unless otherwise indicated. O- benzylhydroxylamine hydrochloride, Oxyma Pure and N,N-diisopropylethylamine (DIPEA), were purchased from Sigma-Aldrich. DFO mesylate was purchased from Abcam. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyri dinium 3-oxid hexafluoroph-osphate (HATU) and H-Lys(Z)-OtBu were purchased from AK Scientific. ZrCl4, EDTA, disodium salt, dihydrate (Molecular biology grade), ammonium acetate, succinic anhydride and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC. HCl) were purchased from Fisher Scientific. Chemical Characterization Methods [00350] 1 H and 13 C NMR spectra were recorded on a 500 MHz Bruker Avance III HD NMR spectrometer at the Saskatchewan Structural Science Centre at the University of Saskatchewan, at 25 ºC in D 2 O, CDCl 3 or (CD 3 ) 2 SO. Chemical shifts were referenced to the residual protons of the deuterated solvents for 1 H NMR ( δ =4.79 ppm for D 2 O; δ =7.26 ppm for CDCl 3 and δ = 2.50 ppm for (CD 3 ) 2 SO. Similarly, 13 C chemical shifts were referenced to the CDCl 3 signal at 77.16 ppm and (CD 3 ) 2 SO signal at δ = 39.52 ppm. Coupling constants are reported to the nearest 0.5 Hz ( 1 H NMR spectroscopy) and for 13 C NMR spectroscopy they are rounded to integer values in Hz. Field desorption ionization (FDI) was used on JEOL AccuTOF GCv 4G mass spectrometer to measure high resolution mass spectra and only the mass peak of the isotope with the highest natural abundance is recorded for the isotopic patterns. Antibody conjugates were analyzed on MALDI-TOF MS/MS using Bruker Ultraflex MALDI-TOF/TOF (Bruker Daltonic GmbH) (Alberta Proteomics and Mass spectrometry Facility, University of Alberta, Canada). HPLC purifications were performed on Thermofisher Vanquish HPLC using C18 reversed- phase column (Inspire Semipreparative DIKMA; 5 µm, 21.2 × 250 mm), a VF-D40-A UV detector, two VF-P10-A pumps and Chromeleon 7 communication software. A flow rate of 4 mL/ minute was used with a gradient of MeCN:H 2 O (with 0.1% formic acid (FA) in both solvents). Low resolution mass spectrometry was performed on Advion Expression- L system (mass range <2000 amu). The Advion Expression-L was coupled with the Thermofisher Vanquish system to perform LCMS. Concentration of antibody mixtures was determined using a Thermofisher NanoDrop UV/Vis instrument. [00351] The synthesis is shown in Scheme 8 and the synthetic details are provided below:

Scheme 8 Synthesis of Tert‐butyl N‐(benzyloxy)carbamate (4) [00352] Compound 4 was prepared according to a published procedure with modification [Bieliauskas AV, Weerasinghe SVW, Negmeldin AT, Pflum MKH. Structural Requirements of Histone Deacetylase Inhibitors: SAHA Analogs Modified on the Hydroxamic Acid. Arch Pharm (Weinheim).2016; 349: 373–82]. O-benzylhydroxylamine hydrochloride (1.00 gm, 6.27mmol) and di-tert-butyl dicarbonate (1.33 mL, 6.23 mmol) were dissolved in THF (7 mL). Then an aqueous solution of sodium hydrogen carbonate (1 M, 7 mL) was added slowly. The reaction was stirred at ambient temperature overnight. The organic solvent was removed by rotary evaporator, then the residue was diluted with water (20 mL) and extracted with dichloromethane (20 mL, 3 times). The organic layers were collected, dried over anhydrous sodium sulfate and then the solvent was removed by rotary evaporator to give the product as a white solid (1.27 gm, 97%), no further purification was required. 1 H NMR [CDCl 3 , 500 MHz]: δ 1.48 (s, 9H, CH 3 ), 4.86 (s, 2H, CH 2 ), 7.1 (s, 1H, NH), 7.3 -7.4 (m, 5H, CH). 13 C NMR [CDCl 3 , 126 MHz]: δ 28.3, 78.5, 81.8, 128.6, 129.2, 135.82, 156.8. HRMS (TOF): m/z Calcd for [C 12 H 17 NO 3 + Na] + :246.1100; found: 246.1103. Synthesis of Tert‐butyl N‐(benzyloxy)‐N‐methylcarbamate (5) [00353] This procedure was adapted from published literature [ Olshvang, E.; Szebesczyk, A.; Kozłowski, H.; Hadar, Y.; Gumienna-Kontecka, E.; Shanzer, A. Biomimetic Ferrichrome: Structural Motifs for Switching between Narrow- and Broad- Spectrum Activities in P. Putida and E. Coli. Dalton Trans.2015, 44 (48)]. Sodium hydride (90%, 197.07 mg, 7.39 mmol) was weighed carefully in a Schlenk flask under nitrogen gas and washed with hexane (4 mL) 3 times. Then anhydrous DMF (15 mL) was added and followed by slow addition of compound 4 (1.50 g, 6.72 mmol). After stirring the mixture for 30 minutes at ambient temperature, iodomethane (0.46 mL, 7.39 mmol) was added and the reaction was left to stir at ambient temperature overnight. The reaction was then quenched by careful addition of water (5 mL) and stirred for 10 minutes. The mixture was further diluted with 20 mL water and extracted with hexane (25 mL, 3 times). The organic layers were pooled, dried over anhydrous sodium sulfate and the solvent was removed by rotary evaporator to give compound 5 as a clear oil (1.54 g, 98%). 1 H NMR [CDCl 3 , 500 MHz]: δ1.49 (s, 9H, CH 3 ), 3.04 (s, 3H, CH 3 ), 4.82 (s, 2H, CH 2 ), 7.31 – 7.41 (m, 5H, CH). 13 C NMR [CDCl 3 , 126 MHz]: δ 28.3, 36.9, 76.6, 81.3, 128.5, 128.6, 129.5, 136.7 and 157.1. HRMS (TOF): m/z Calcd for [C 13 H 19 NO 3 + H] + : 238.1437; found: 238.1432. Synthesis of (benzyloxy)(methyl)amine (6) [00354] This Boc-deprotection procedure was modified from published procedure [ Gudmundsdottir AV, Paul CE, Nitz M. Stability studies of hydrazide and hydroxylamine- based glycoconjugates in aqueous solution. Carbohydr Res.2009; 344: 278–84]. To a solution of compound 5 (1.49 g, 6.28 mmol) in dichloromethane (7.5 mL), trifluoroacetic acid (7.5 mL, 97.32 mmol) was added and stirred for 5 h at ambient temperature. A saturated sodium hydrogen carbonate solution (20 mL) was added and extracted with dichloromethane (20 mL, 3 times). The organic layers were collected and dried over anhydrous sodium sulfate. The solvent was evaporated via rotary evaporator and the crude product mixture was purified with column chromatography (30% ethyl acetate in hexane). Compound 6 was obtained (0.79 g, 92%) as a clear oil. 1 H NMR [CDCl 3 , 500 MHz]: δ 2.74 (s, 3H, CH 3 ), 4.73 (2H, CH 2 ), 5.56 (s, 1H, NH), 7.31 – 7.41 (m, 5H, CH). 13 C NMR [CDCl 3 , 126 MHz]: δ 39.3, 75.6, 127.8, 128.3, 128.4, 138.0. HRMS (TOF): m/z Calcd for [C 18 H 11 NO + H] + : 138.0913; found: 138.0908. Synthesis of Compound (7) [00355] Compound 7 was synthesized based on a published procedure with modifications [Olshvang, E.; Szebesczyk, A.; Kozłowski, H.; Hadar, Y.; Gumienna- Kontecka, E.; Shanzer, A. Biomimetic Ferrichrome: Structural Motifs for Switching between Narrow- and Broad-Spectrum Activities in P. Putida and E. Coli. Dalton Trans. 2015, 44 (48)]. Succinic anhydride (2.19 g, 21.9 mmol) was added to a mixture of 6 (1.00 g, 7.29 mmol) and triethylamine (2.0 mL, 14.34 mmol) in THF (16 mL). The reaction mixture was stirred overnight at ambient temperature. After the reaction completion was confirmed with TLC (50% ethyl acetate in hexane, Rf = 0.28), the solvent was evaporated, and the residue was dissolved in aqueous sodium hydroxide (30 mL, 0.5 M). The solution was washed with diethyl ether (20 mL × 2). Then the solution was acidified to pH ~ 2 with hydrochloric acid and the product was extracted with dichloromethane (40 mL × 3). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporator to give compound 7 (1.29 g, 75%). 1 H NMR [CDCl 3 , 500 MHz]: δ 2.62 (t, J=6.5 Hz, 2H, CH 2 ), 2.72 (t, J=6.4 Hz, 2H, CH 2 ), 3.19 (s, 3H, CH 3 ), 4.81 (s, 2H, CH 2 ), 7.32-737 (m, 5H, CH Ar), 10.93 (s, 1H, OH). 13 C NMR [CDCl 3 , 126 MHz]: δ 27.0, 28.6, 76.2, 128.7, 129.3, 134.2, 173.6, 177.6. HRMS: m/z Calcd for [C 12 H 15 NO 4 + H] + : 238.1074; found: 238.1082. Synthesis of Compound (8) [00356] To solution of 7 (500.20 mg, 2.11 mmol) in DMF (15 mL), Oxyma (331.1 mg, 2.33 mmol), EDC (448.1 mg, 2.32 mmol), and N,N-diisopropylethylamine (1.1 mL, 6.32 mmol) were added. The mixture was stirred for 20 minutes at ambient temperature before H-Lys(Z)-OtBu HCl (851.4 mg, 2.28 mmol) was added, and the reaction was stirred overnight at ambient temperature. Then the reaction mixture was added to water (50 mL) and extracted with dichloromethane (30 mL × 4). The combined organic layers were collected and washed with water, dried with anhydrous sodium sulfate. The solvent was removed by using rotary evaporator and the obtained crude product mixture was purified with column chromatography (50% ethyl acetate in hexane, Rf = 0.21) to give compound 8 (809.7 mg, 69%). 1 H NMR [CDCl 3 , 500 MHz]: δ 1.34-1.41 (m, 2H, CH 2 ), 1.44 (s, 9H, CH 3 ), 1.50 (quint, J=7.0, 2H, CH 2 ), 1.58-1.86 (m, 2H, CH 2 ), 1.50 (quint, J=7.0 Hz, 2H, CH 2 ), 2.45-2.48 (m, 2H, CH 2 ), 2.67-2.84 (m, 2H, CH 2 ), 3.1 (s, 3H, CH 3 ), 3.14-3.22 (m, 2H, CH 2 ), 4.43, 4.48 (m, 1H, CH), 4.82 (s, 2H, CH 2 ), 5.06 (q, J=11.4 Hz, 2H, CH 2 ), 5.31 (br s, 1H, NH), 6.45 (d, J=7.8 Hz, 1H, NH), 7.27-7.32 (m, 5H, CH), 7.36-7.38 (m, 5H, CH). 13 C NMR [CDCl 3 , 126 MHz]: δ 22.3, 27.7, 28.0, 29.2, 30.5, 32.1, 40.5, 66.5, 76.3, 81.9, 128.0, 128.1, 128.5, 128.7, 129.0, 129.3, 156.6, 171.6, 171. 9. HRMS: m/z Calcd for [C 30 H 41 N 3 O 7 + H] + : 556.3017; found: 556.2992. Synthesis of Compound (9) [00357] This procedure was modified from a published procedure [Gudmundsdottir AV, Paul CE, Nitz M. Stability studies of hydrazide and hydroxylamine-based glycoconjugates in aqueous solution. Carbohydr Res.2009; 344: 278–84]. Compound 8 (1.11 g, 2.00 mmol) was dissolved in a mixture of TFA (2.5 mL, 32.7 mmol) and dichloromethane (5 mL). The reaction was stirred for 6 hours at RT. Then the volatiles were removed by using rotary evaporator and the crude mixture was purified through column chromatography (10% methanol in ethyl acetate, Rf = 0.4) to give compound 9 (0.73 g, 74%). 1 H NMR [CDCl 3 , 500 MHz]: δ 1.36-1.1.50 (m, 4H, CH 2 ), 1.66-1.92 (m, 2H, CH 2 ), 2.51 (br s, 2H, CH 2 ), 2.77 (br s, 2H, CH 2 ), 3.11 (s, 3H, CH 3 ), 3.15-3.19 (m, 2H, CH 2 ), 4.54 (q, J=6.7 Hz, 1H, CH), 4.82 (s, 2H, CH 2 ), 5.03-5.12 (m, 2H, CH 2 ). 7.03 (br s, 1H, NH), 7.28 – 7.36 (m, 10H, CH), 10.17 (br s, 1H, OH). 13 C NMR [CDCl 3 , 126 MHz]: δ 22.3, 27.7, 29.3, 30.4, 31.4, 33.7, 40.6, 52.3, 66.7, 76.4, 128.1, 128.2, 128.6, 128.8, 129.1, 129.4, 134.3, 136.7, 156.9, 173.1, 174.2, 174.8. HRMS: m/z Calcd for [C 26 H 33 N 3 O 7 + H] + : 500.2391; found: 500.2410. Synthesis of Compound (10) [00358] A solution of HATU (0.27 g, 0.71 mmol) and DIPEA (0.35 mL, 0.70 mmol) in 14 mL DMF was added to a solution of 9 (0.30 g, 0.60 mmol) in 13 mL DMF and the mixture was stirred for 10 minutes at ambient temperature. DFO mesylate (0.44 g, 0.67 mmol) was dissolved in 10 mL DMF and 4 mL DMSO (at 80 ºC). Once fully dissolved, the DFO mixture was allowed to cool for few minutes ( ~ 50 ºC), it was then added to the above solution of the activated ester. The reaction was left to stir overnight at ambient temperature. Then the reaction mixture was condensed to ~ 2 mL by using rotary evaporator and the residue was added dropwise to ~ 70 mL ethyl acetate spread into 2 falcon tubes (50 mL size tubes). The tubes were kept in a spark proof -20 ºC freezer until maximum amount of precipitate was formed (overnight). The precipitate was separated by decantation after centrifugation (4000 rpm, 15 minutes) and washed two times with cold ethyl acetate. The crude was then purified by using reverse phase column chromatography (Biotage Isolera) (10 -100% acetonitrile in water) to collect 10 (316 mg, 50%) as an off-white powder. 1 H NMR [(CD 3 ) 2 SO, 500 MHz]: δ 1.19 – 1.67 (m, 28H, CH 2 ), 1.96 (s, 3H, CH 3 ), 2.26 (t, J= 7.3 Hz, 4H, CH 2 ), 2.31-2.38 (m, 2H, CH 2 ), 2.57 (t, J=6.9 Hz, 4H, CH 2 ), 2.65 (br s, 2H, CH 2 ), 2.9-3.00 (m, 8H, CH 2 ), 3.12 (s, 3H, CH 3 ), 3.44 (q, J=6.6 Hz, 6H, CH 2 ), 4.08-4.13 (m, 1H, CH), 4.90 (s, 2H, CH 2 ), 4.99 (s, 2H, CH 2 ), 7.22 (t, J=5.6 Hz, 1H, NH), 7.30-7.45 (m, 10H, CH), 7.76 (t, J=5.5 Hz, 1H, NH), 7.82 (br s, 2H, NH), 8.00 (br d, J=8, 1H, NH), 9.74 (br s, 3H, OH). 13 C NMR [(CD 3 ) 2 SO, 126 MHz]: δ 22.8, 23.1, 23.5, 26.0, 27.1, 27.6, 28.7, 28.8, 29.1, 29.6, 30.0, 31.6, 38.4, 46.8, 47.1, 65.1, 127.7, 128.4, 128.5, 128.7, 129.4, 137.3, 156.1, 171.3, 171.6, 171.9. HRMS: m/z Calcd for [C 51 H 79 N 9 O 14 + H] + : 1042.5825; found: 1042.5819. Synthesis of Compound DFO-Km [00359] In a Schlenk flask, 10% Palladium on carbon (25.0 mg, 23.5 μmol) was added to a solution of compound 10 (120.0 mg, 115 μmol) in 20 mL methanol. The flask was sealed with a rubber septa and connected to an H 2 gas balloon fitted with a glass stopcock and a needle, and the flask was additionally connected to vacuum via Schlenk line. The flask was put under vacuum for 15 seconds and then the vacuum was closed, and the flask was purged with H 2 gas by slowly opening the glass stopcock valve. The vacuum and purging were repeated 4 times and finally the flask was left stirring under H 2 for 2 hours. Then the reaction solution was filtered through celite to remove the Pd/C, and the solvent was evaporated by using rotary evaporator. The crude product mixture was purified by using semipreparative RP-HPLC. HPLC conditions: C18 Inspire Semipreparative DIKMA; 5 µm, 21.2 × 250 mm; (20 – 32% acetonitrile in water (0.1% formic acid); flow rate, 4 mL/min, t R = 15 min) to give DFO-Km (I-7) (83.5 mg, 68%) as white powder. 1 H NMR [D 2 O, 500 MHz]: δ 1.20-1.84 (m, 24H, CH 2 ), 2.10 (s, 3H, CH 3 ), 2.44-2.53 (m, 6H, CH 2 ), 2.62-2.81 (m, 6H, CH 2 ), 2.96 (t, J=7.6 Hz, 2H, CH 2 ), 3.12-3.16 (m, 6H, CH 2 ), 3.19 (s, 3H, CH 3 ), 3.55-3.62 (m, 6H, CH 2 ), 4.16 (q, J=4.8, 1H, CH). 13 C NMR [D 2 O, 126 MHz]: δ 19.3, 22.1, 23.0, 25.4, 26.2, 27.1, 27.6, 27.8, 28.0, 29.8, 30.3, 30.4, 30.7, 35.8, 39.1, 47.6, 47.8, 51.0, 51.5, 53.8, 170.8, 173.5, 173.8, 173.9, 174.7, 175.4. HRMS: m/z Calcd for [C 36 H 67 N 9 O 12 + H] + : 818.4982; found: 818.4942. Example 4: Preparation of DFO-PyrZW-p-SCN-Ph The preparation of DFO- PyrZW-p-SCN-Ph is shown in Scheme 9 and the synthetic details are provided below: Synthesis of R10 (step a): [00360] Fmoc-Ala-PyrZW-OH (100 mg, 0.2 mmol) was dissolved in DMF (2.0 ml). To this, 1 eq. of DCC (41.3 mg) and 1 eq. NHS (23.0 mg) were added and the reaction mixture was stirred for 4 hours at room temperature. The by-product precipitate was filtered out and the filtrate concentrated and left on high-vacuum overnight. The oily product was dried by dissolving it in CHCl 3 and hexane and removing solvent under partial vacuum with a rotary evaporator a 2-3 times until it gives a dry white powder (81.86 mg, 67.4% yield). Calculated mass for C 30 H 29 N 3 O 9 S was 607.63, found 608.3 m/z. Synthesis of R11 (steps b and c): [00361] Fmoc-PyrZW-NHS (20.0 mg, 0.033 mmol) was dissolved in dry DMF (0.5 ml) in a round bottom flask equipped with a stirring bar. DFO mesylate (18.5 mg, 0.033 mmol, 1 eq.) was dissolved in DMF (0.3 ml) and DMSO (0.2 ml) heating in an oil bath at 75 degree celsius until the solution was clear, and it was added to the round bottom flask containing PyrZW-NHS in one portion. The reaction mixture was left to react overnight at room temperature. The crude reaction mixture was then checked with LRMS. Calculated mass for C51H72N8O14S was 1053.24, found 527.12 [M+2H] +, and 1053.4 m/z. [00362] The crude product was concentrated to remove the solvent by cold-finger before its purification on a C18 column (20% CH 3 CN:H 2 O gradient). [00363] DFO-PyrZW was obtained as shown in step c) on scheme 9 above and the final product DFO- PyrZW-p-SCN-Ph was obtained as shown in step d) on scheme 9 above.

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