EXTRACELLULAR HSP90 (eHSP90)-TARGETED RADIOPHARMACEUTICALS AND USE THEREOF RELATED APPLICATION [1] The present application claims priority to U.S. Provisional Application No.63/401,227, filed on August 26, 2022, the entire contents of which are hereby incorporated by reference for all purposes. BACKGROUND [2] Heat shock protein 90 (HSP90) is a molecular chaperone that regulates protein folding to ensure correct conformation and translocation and to avoid protein aggregation. Many oncogenic proteins are HSP90 client proteins, such as epidermal growth factor receptor (EGFR) mutant, cyclin dependent kinase 4 (CDK4), hypoxia-inducible factor (HIF)-1Į, and matrix metallopeptidase 2 (MMP2). [3] There is a fraction of HSP90 identified at the surface of a number of cell types, i.e., extracellular HSP90 (eHSP90), which can be a useful tumor antigen for eliciting a host immune response. Studies show that eHSP90 plays a crucial role in maintaining oncogenic protein homoeostasis and participates in the invasion and metastatic processes of various cancers including breast cancer, which make eHSP90 an attractive target for developing cancer therapy. [4] HSP90 inhibition has been shown to have a significant direct impact on cell cycle and DNA repair mechanisms, thus offering great promise in the treatment of a wide variety of solid and hematological malignancies. However, early clinical trials have demonstrated that certain HSP90 inhibitors exhibited limited efficacy and various side effects. [5] Therefore, there is a need for improved treatment of cancers with good efficacy and acceptable safety profiles by targeting certain proteins, e.g., eHSP90. SUMMARY [6] The present disclosure encompasses the insight that certain radiopharmaceuticals comprising a targeting moiety that specifically binds to HSP90, in particular, eHSP90, can be effective as HSP90 radioligand therapy (RLT) for treating cancers. Radioactive decay can cause direct physical damage (such as single or double-stranded DNA breaks) or indirect damage (such as by-stander or crossfire effects) to the biomolecules that constitute a cell. Drugs that deliver radionuclides to cancer cells, i.e., radiopharmaceuticals, provide a mechanism to generate DNA damage with anti-cancer therapeutic effect. The present disclosure provides certain radiopharmaceuticals, specifically, small molecule-based radiopharmaceuticals targeting HSP90- overexpressing tumors and using actinium-225 ( ²²⁵ Ac), lutetium-177 ( ¹⁷⁷ Lu) or other suitable therapeutic radionuclides to target cancer cells to treat or ameliorate cancers such as lung cancer, sarcoma, pancreatic cancer, breast cancer, or colon cancer. [7] In one aspect, the present disclosure provides compounds of Formula I, or a pharmaceutically acceptable salt thereof: Z ^{1 X} N Y Z ² n W HO HN N O OH N N (I), wherein X is absent, C=O, or (C=O)NR ¹ , R ¹ being H, alkyl, aryl, (C-CF ₃ )R ² or (SO ₂ )R ² , R ² being alkyl or aryl; Y is each independently O or NR ³ , R ³ being H, alkyl, aryl, or acyl; n is an integer of 0-5 (inclusive); Z ¹ and Z ² each are, independently, absent, an amino acid unit, (C=O)NR ⁴ (CH2CH2)O, or (C=O)NR ⁴ (CH2CH2)NR ⁵ , in which each of R ⁴ and R ⁵ independently is H or alkyl or (C-CF3)R ⁶ or (SO2)R ⁶ , R ⁶ being alkyl or aryl; and W is a chelator selected from the group consisting of DOTA, DOTAGA, NOTA, and NODAGA, each as defined in the DETAILED DESCRIPTION section below, wherein when W is DOTA, at least one of Z ¹ and Z ² is an amino acid unit, or each of Z ¹ and Z ² is absent and n is equal to or less than 4; wherein the compound binds to HSP90; and wherein the compound optionally further comprises a radionuclide chelated by the chelator. [8] In some embodiments, the compounds of this disclosure specifically bound to extracellular HSP90 (eHSP90). [9] In some embodiments, the compounds of this disclosure have the structure of Formula II: O HO O N N HO O Z ¹ OH X N N N Y Z ² n O O ^OH HO HN N O N N OH (II), wherein each of X, Y, n, Z ¹ , and Z ² is as defined above. [10] In some embodiments, the compounds of Formula I or Formula II feature that at least one of Z ¹ and Z ² is an amino acid unit. [11] In some embodiments, the compounds of Formula I or Formula II feature that the amino acid unit is formed from glycine (Gly), aspartic acid (Asp), glutamic acid (Glu), 2,4- diaminobutyric acid (Dab), 2,3-diaminopropionic acid (Dap), lysine (Lys), or arginine (Arg). [12] In some embodiments, the compounds of Formula I or Formula II feature that the amino acid unit is formed from glycine (Gly), aspartic acid (Asp), glutamic acid (Glu), 2,4- diaminobutyric acid (Dab), 2,3-diaminopropionic acid (Dap), lysine (Lys), arginine (Arg), or combination thereof. [13] In some embodiments, the compounds of Formula I or Formula II feature that the amino acid unit comprises an organic moiety formed from Asp. [14] In some embodiments, the compounds of Formula I or Formula II feature that the amino acid unit is formed from Gly. [15] In some embodiments, the compounds of Formula I or Formula II feature that the amino acid unit is formed from Glu. [16] In some embodiments, the compounds of Formula I or Formula II feature that X is absent. [17] In some embodiments, the compounds of Formula I or Formula II feature that X is C=O. [18] In some embodiments, the compounds of Formula I or Formula II feature that X is (C=O)NR ¹ , wherein R ¹ is H, alkyl, or aryl. [19] In some embodiments, the compounds of Formula I or Formula II feature that X is (C=O)NH. [20] In some embodiments, the compounds of Formula I or Formula II feature that n is 0. [21] In some embodiments, the compounds of Formula I or Formula II feature that n is 1, 2, or 3. [22] In some embodiments, the compounds of Formula I or Formula II feature that n is 4 or 5. [23] In some embodiments, the compounds of Formula I or Formula II feature that n is 4. [24] In some embodiments, the compounds of Formula I or Formula II feature that n is 5. [25] In some embodiments, the compounds of Formula I or Formula II feature that Y is each independently O, NH, or N(C1-6 alkyl). In some embodiments, the compounds of Formula I or Formula II feature that Y is each independently O. In some embodiments, the compounds of Formula I or Formula II feature that Y is each independently NH. [26] In some embodiments, the compounds of Formula I or Formula II feature that each of Z ¹ and Z ² is absent. [27] In some embodiments, the compounds of Formula I or Formula II feature that Z ¹ is absent. [28] In some embodiments, the compounds of Formula I or Formula II feature that Z ² is absent. [29] In some embodiments, the compounds of Formula I or Formula II feature that Z ¹ is an amino acid unit. [30] In some embodiments, the compounds of Formula I or Formula II feature that Z ² is an amino acid unit. [31] In some embodiments, the compounds of Formula I or Formula II feature that Z ¹ is (C=O)NH(CH ₂ CH ₂ )NH. In some embodiments, the compounds of Formula I or Formula II feature that Z ² is (C=O)NH(CH ₂ CH ₂ )NH. [32] In some embodiments, the compounds of Formula I or Formula II feature that Z ¹ is (C=O)NH(CH2CH2)N(C1-6 alkyl). In some embodiments, the compounds of Formula I or Formula II feature that Z ² is (C=O)NH(CH2CH2)N(C1-6 alkyl). [33] In some embodiments, the compounds of Formula I or Formula II feature that Z ¹ is (C=O)N(C _1-6 alkyl)(CH ₂ CH ₂ )NH. In some embodiments, the compounds of Formula I or Formula II feature that Z ² is (C=O)N(C _1-6 alkyl)(CH ₂ CH ₂ )NH. [34] In some embodiments, the compounds of Formula I or Formula II feature that Z ¹ is (C=O)N(C1-6 alkyl)(CH2CH2)N(C1-6 alkyl). In some embodiments, the compounds of Formula I or Formula II feature that Z ² is (C=O)N(C1-6 alkyl)(CH2CH2)N(C1-6 alkyl). [35] In some embodiments, the compounds of Formula I or Formula II feature that X is absent, n is 0, Z ¹ is absent, and Z ² is an amino acid unit. [36] In some embodiments, the compounds of Formula I or Formula II feature that X is C=O, n is 4 or 5, Z ¹ is an amino acid unit, and Z ² is absent. [37] In some embodiments, the compounds of Formula I or Formula II feature that X is C=O, n is 4 or 5, Z ¹ is absent, and Z ² is an amino acid unit. [38] In some embodiments, the amino acid unit is selected from the group consisting of HO O O OH O H N N O H H O N O H N N H , O , HO O , ^{H2N O} , HO O O OH O H O O _H ^O H N H N N N N N H N H O H O O HN HO O HN H ₂ N NH , NH ₂ , H ₂ N NH and HO O O O H H N N N H O H ₂ N O HN H ₂ N NH . [39] In some embodiments, the compounds of Formula I or Formula II feature that X is (C=O)NH, n is 4 or 5, each of Z ¹ and Z ² is absent. [40] In some embodiments, the compounds of Formula I or Formula II feature that X is C=O, n is 4 or 5, Z ¹ is absent, and Z ² is (C=O)NH(CH2CH2)NH. [41] In some embodiments, the compounds of Formula I or Formula II feature that X is absent, n is 0, each of Z ¹ and Z ² is absent. [42] In some embodiments, the compounds of Formula I or Formula II are selected from the group consisting of: O HO O N N HO O O OH O O N N N O O N H O O ^OH HO HN N O N N OH , HO O O N N HO O H O OH (S) N O O N N N O N H O O CO ₂ H _O ^OH HO HN N O OH N N , O HO O N N HO O H O OH (S) N O O N N N O N H O O CO ₂ H HO HN N O OH N N ,

O HO O N N H ^O HO O ₂ ^C O H OH O N N N N O O _(S) ^N H O O O OH HO HN N O N N OH , O HO O N N H ^O HO O _2C O H OH O N N N N O O _(S) ^N H O O HO HN N O N N OH , O OH O H O N O N _O ^O N _O N N H O OH HO N N O HO O HO HN N O OH N N , O H O N O O ^O N N _O H ^{N N} O _OH HO N N O HO O HO HN N O OH N N , HO O O N N HO O H H O OH O N N N N N ^O _O N O H O O ^OH HO HN N O OH N N , HO O O N N HO O H H O OH N N N N ^{O O} _O N N O H O HO HN N O N N OH , O ^O _OH H N O (S) N N N O OH CO ₂ H HO N N O HO O HO HN N O N N OH , O O H N OH (S) N N N O N CO ₂ H HO N HO O O HO HN N O N N OH ,

O O HO HO O O N N N N HO HO O OH O OH N N N N N O N O O ^OH HO HN HO HN N N O O N N N N OH , and OH . [43] In some embodiments, the compounds of Formula I or Formula II feature that each compound comprises a radionuclide selected from the group consisting of ⁴³ Sc, ⁴⁴ Sc, ⁴⁷ Sc, ⁵⁵ Co, ⁶⁰ Cu, ⁶¹ Cu, ⁶² Cu, ⁶⁴ Cu, ⁶⁷ Cu, ⁶⁶ Ga, ⁶⁷ Ga, ⁶⁸ Ga, ⁸² Rb, ⁸⁶ Y, ⁸⁷ Y, ⁸⁹ Zr, ⁹⁰ Y, ⁹⁷ Ru, ⁹⁹ Tc, ^99m Tc, ¹⁰⁵ Rh, ¹⁰⁹ Pd, ¹¹¹ In, ^117m Sn, ¹³³ La, ¹³⁴ Ce, ¹⁴⁹ Pm, ¹⁴⁹ Tb, ¹⁵³ Sm, ¹⁵² Tb, ¹⁵⁵ Tb, ¹⁶¹ Tb, ¹⁶⁶ Ho, ¹⁷⁷ Lu, ¹⁸⁶ Re, ¹⁸⁸ Re, ¹⁹⁸ Au, ¹⁹⁹ Au, ²⁰¹ Tl, ²⁰³ Pb, ²¹¹ At, ²¹² Pb, ²¹² Bi, ²¹³ Bi, ²²³ Ra, ²²⁵ Ac, ²²⁷ Th, and ²²⁹ Th. [44] In certain embodiments, the radionuclide is selected from the group consisting of ⁶⁸ Ga, ⁸⁹ Zr, ⁹⁰ Y, ¹¹¹ In, ¹⁷⁷ Lu, and ²²⁵ Ac. [45] In certain embodiments, the radionuclide is ¹⁷⁷ Lu or ²²⁵ Ac. [46] In certain embodiments, the radionuclide is ¹⁷⁷ Lu. [47] In certain embodiments, the radionuclide is ²²⁵ Ac. [48] In another aspect, the present disclosure also covers a pharmaceutical composition comprising one of the compounds set forth above and a pharmaceutically acceptable excipient. [49] Still within the scope of this disclosure is a method of treating cancer, the method comprising administering to a subject in need thereof one of the compounds set forth above or the above-described pharmaceutical composition. [50] In some embodiments, the method of treating cancer comprises administering to the subject in need thereof a first dose of one of the compounds or the composition described above in an amount effective for radiation treatment planning, followed by administering subsequent doses of one of the compounds or the composition described above in a therapeutically effective amount. [51] In some embodiments, the cancer is small-cell lung cancer, non-small-cell lung cancer, sarcoma, pancreatic cancer, breast cancer, or colon cancer. BRIEF DESCRIPTION OF THE DRAWINGS [52] FIG.1. Tumor growth of HSP90 expressing xenograft tumors in response to treatment with 225Ac-Compound D. DETAILED DESCRIPTION [53] The present disclosure relates to radiopharmaceutical compounds comprising a targeting moiety that specifically binds to HSP90, in particular, extracellular HSP90 (eHSP90). [54] Radio-labelled targeting molecules (also known as radiopharmaceuticals) are designed to target a protein or receptor (e.g., eHSP90) that is upregulated in a disease state and/or specific to diseased cells (e.g., tumor cells) to deliver a radioactive payload to damage and kill cells of interest. Radiopharmaceuticals targeting eHSP90 provided in this disclosure can be used for treating various cancers including, but not limited to, small-cell lung cancer, non-small-cell lung cancer, sarcoma, pancreatic cancer, breast cancer, and colon cancer. Definitions Chemical Terms [55] The term “alkyl,” as used herein, is inclusive of both straight chain and branched chain saturated groups from 1 to 20 carbons (e.g., from 1 to 10 or from 1 to 6), unless otherwise specified. Alkyl groups are exemplified by methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl, neopentyl, and the like, and may be optionally substituted with one, two, three, or, in the case of alkyl groups of two carbons or more, four substituents independently selected from the group consisting of: (1) C _1-6 alkoxy; (2) C _1-6 alkylsulfinyl; (3) amino, as defined herein (e.g., unsubstituted amino (i.e., -NH ₂ ) or a substituted amino (i.e., -N(R ^N1 ) ₂ , where R ^N1 is as defined for amino); (4) C _6-10 aryl-C _1-6 alkoxy; (5) azido; (6) halo; (7) (C _2-9 heterocyclyl)oxy; (8) hydroxy, optionally substituted with an O-protecting group; (9) nitro; (10) oxo (e.g., carboxyaldehyde or acyl); (11) C1-7 spirocyclyl; (12) thioalkoxy; (13) thiol; (14) -CO2R ^A’ , optionally substituted with an O-protecting group and where R ^A’ is selected from the group consisting of (a) C1-20 alkyl (e.g., C1-6 alkyl), (b) C2-20 alkenyl (e.g., C2-6 alkenyl), (c) C6-10 aryl, (d) hydrogen, (e) C1-6 alk-C6-10 aryl, (f) amino-C _1-20 alkyl, (g) polyethylene glycol of -(CH ₂ ) _s2 (OCH ₂ CH ₂ ) _s1 (CH ₂ ) _s3 OR’, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R’ is H or C1-20 alkyl, and (h) amino-polyethylene glycol of - NR ^N1 (CH2)s2(CH2CH2O)s1(CH2)s3NR ^N1 , wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R ^N1 is, independently, hydrogen or optionally substituted C _1-6 alkyl; (15) -C(O)NR ^B’ R ^C’ , where each of R ^B’ and R ^C’ is, independently, selected from the group consisting of (a) hydrogen, (b) C _1-6 alkyl, (c) C _6-10 aryl, and (d) C1-6 alk-C6-10 aryl; (16) -SO2R ^D’ , where R ^D’ is selected from the group consisting of (a) C1-6 alkyl, (b) C6-10 aryl, (c) C1-6 alk-C6-10 aryl, and (d) hydroxy; (17) -SO2NR ^E’ R ^F’ , where each of R ^E’ and R ^F’ is, independently, selected from the group consisting of (a) hydrogen, (b) C1-6 alkyl, (c) C6-10 aryl and (d) C1-6 alk-C6-10 aryl; (18) -C(O)R ^G’ , where R ^G’ is selected from the group consisting of (a) C _1-20 alkyl (e.g., C _1-6 alkyl), (b) C _2-20 alkenyl (e.g., C _2-6 alkenyl), (c) C _6-10 aryl, (d) hydrogen, (e) C _1-6 alk-C _6-10 aryl, (f) amino-C _1-20 alkyl, (g) polyethylene glycol of - (CH ₂ ) _s2 (OCH ₂ CH ₂ ) _s1 (CH ₂ ) _s3 OR’, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R’ is H or C1-20 alkyl, and (h) amino-polyethylene glycol of -NR ^N1 (CH2)s2(CH2CH2O)s1(CH2)s3NR ^N1 , wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R ^N1 is, independently, hydrogen or optionally substituted C _1-6 alkyl; (19) -NR ^H’ C(O)R ^I’ , wherein R ^H’ is selected from the group consisting of (a1) hydrogen and (b1) C _1-6 alkyl, and R ^I’ is selected from the group consisting of (a2) C _1-20 alkyl (e.g., C _1-6 alkyl), (b2) C _2-20 alkenyl (e.g., C _2-6 alkenyl), (c2) C _6-10 aryl, (d2) hydrogen, (e2) C _1-6 alk-C _6-10 aryl, (f2) amino-C _1-20 alkyl, (g2) polyethylene glycol of -(CH2)s2(OCH2CH2)s1(CH2)s3OR’, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R’ is H or C1-20 alkyl, and (h2) amino- polyethylene glycol of -NR ^N1 (CH2)s2(CH2CH2O)s1(CH2)s3NR ^N1 , wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R ^N1 is, independently, hydrogen or optionally substituted C _1-6 alkyl; (20) -NR ^J’ C(O)OR ^K’ , wherein R ^J’ is selected from the group consisting of (a1) hydrogen and (b1) C1-6 alkyl, and R ^K’ is selected from the group consisting of (a2) C1-20 alkyl (e.g., C1-6 alkyl), (b2) C2-20 alkenyl (e.g., C2-6 alkenyl), (c2) C6-10 aryl, (d2) hydrogen, (e2) C1-6 alk-C6-10 aryl, (f2) amino-C1-20 alkyl, (g2) polyethylene glycol of -(CH2)s2(OCH2CH2)s1(CH2)s3OR’, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R’ is H or C _1-20 alkyl, and (h2) amino- polyethylene glycol of -NR ^N1 (CH ₂ ) _s2 (CH ₂ CH ₂ O) _s1 (CH ₂ ) _s3 NR ^N1 , wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R ^N1 is, independently, hydrogen or optionally substituted C1-6 alkyl; and (21) amidine. In some embodiments, each of these groups can be further substituted as described herein. For example, the alkylene group of a C1-alkaryl can be further substituted with an oxo group to afford the respective aryloyl substituent. [56] The terms “alkylene”, “alkylidene”, and the prefix “alk-,” as used herein, represent a saturated divalent hydrocarbon group derived from a straight or branched chain saturated hydrocarbon by the removal of two hydrogen atoms, and is exemplified by methylene, ethylene, isopropylene, and the like. The terms “Cx-y alkyl,” “Cx-y alkylene,” “Cx-y alkylidene,” and the prefix “Cx-y alk-” represent alkyl or alkylene groups having between x and y carbons. Exemplary values for x are 1, 2, 3, 4, 5, and 6, and exemplary values for y are 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, or 20 (e.g., C1-6, C1-10, C2-5, C2-8, C2-10, or C2-20 alkyl or alkylene). In some embodiments, the alkylene can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein for an alkyl group. [57] The term “alkenyl,” as used herein, represents monovalent straight or branched chain groups of, unless otherwise specified, from 2 to 20 carbons (e.g., from 2 to 6 or from 2 to 10 carbons) containing one or more carbon-carbon double bonds and is exemplified by ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, and the like. Alkenyls include both cis and trans isomers. Alkenyl groups may be optionally substituted with 1, 2, 3, or 4 substituent groups that are selected, independently, from amino, aryl, cycloalkyl, or heterocyclyl (e.g., heteroaryl), as defined herein, or any of the exemplary alkyl substituent groups described herein. [58] The term “alkynyl,” as used herein, represents monovalent straight or branched chain groups from 2 to 20 carbon atoms (e.g., from 2 to 4, from 2 to 6, or from 2 to 10 carbons) containing a carbon-carbon triple bond and is exemplified by ethynyl, 1-propynyl, and the like. Alkynyl groups may be optionally substituted with 1, 2, 3, or 4 substituent groups that are selected, independently, from aryl, cycloalkyl, or heterocyclyl (e.g., heteroaryl), as defined herein, or any of the exemplary alkyl substituent groups described herein. [59] The term “amino,” as used herein, represents –N(R ^N1 ) ₂ , wherein each R ^N1 is, independently, H, OH, NO ₂ , N(R ^N2 ) ₂ , SO ₂ OR ^N2 , SO ₂ R ^N2 , SOR ^N2 , an N-protecting group, alkyl, alkenyl, alkynyl, alkoxy, aryl, alkaryl, cycloalkyl, alkcycloalkyl, carboxyalkyl (e.g., optionally substituted with an O-protecting group, such as optionally substituted arylalkoxycarbonyl groups or any described herein), sulfoalkyl, acyl (e.g., acetyl, trifluoroacetyl, or others described herein), alkoxycarbonylalkyl (e.g., optionally substituted with an O-protecting group, such as optionally substituted arylalkoxycarbonyl groups or any described herein), heterocyclyl (e.g., heteroaryl), or alkheterocyclyl (e.g., alkheteroaryl), wherein each of these recited R ^N1 groups can be optionally substituted, as defined herein for each group; or two R ^N1 combine to form a heterocyclyl or an N- protecting group, and wherein each R ^N2 is, independently, H, alkyl, or aryl. Amino groups can be unsubstituted amino (i.e., –NH ₂ ) or substituted amino (i.e., –N(R ^N1 ) ₂ ) groups. In a preferred embodiment, amino is –NH2 or –NHR ^N1 , wherein R ^N1 is, independently, OH, NO2, NH2, NR ^N2 2, SO2OR ^N2 , SO2R ^N2 , SOR ^N2 , alkyl, carboxyalkyl, sulfoalkyl, acyl (e.g., acetyl, trifluoroacetyl, or others described herein), alkoxycarbonylalkyl (e.g., t-butoxycarbonylalkyl) or aryl, and each R ^N2 can be H, C1-20 alkyl (e.g., C1-6 alkyl), or C6-10 aryl. [60] The term “amino acid,” as described herein, refers to a molecule having a side chain, an amino group, and an acid group (e.g., a carboxy group of –CO ₂ H or a sulfo group of –SO ₃ H), wherein the amino acid is attached to the parent molecular group by the side chain, amino group, or acid group (e.g., the side chain). In some embodiments, the amino acid is attached to the parent molecular group by a carbonyl group, where the side chain or amino group is attached to the carbonyl group. Exemplary side chains include an optionally substituted alkyl, aryl, heterocyclyl, alkaryl, alkheterocyclyl, aminoalkyl, carbamoylalkyl, and carboxyalkyl. Exemplary amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, hydroxynorvaline, isoleucine, leucine, lysine, methionine, norvaline, ornithine, phenylalanine, proline, pyrrolysine, selenocysteine, serine, taurine, threonine, tryptophan, tyrosine, and valine. Amino acid groups may be optionally substituted with one, two, three, or, in the case of amino acid groups of two carbons or more, four substituents independently selected from the group consisting of: (1) C1-6 alkoxy; (2) C1-6 alkylsulfinyl; (3) amino, as defined herein (e.g., unsubstituted amino (i.e., -NH2) or a substituted amino (i.e., -N(R ^N1 )2, where R ^N1 is as defined for amino); (4) C6-10 aryl-C1-6 alkoxy; (5) azido; (6) halo; (7) (C _2-9 heterocyclyl)oxy; (8) hydroxy; (9) nitro; (10) oxo (e.g., carboxyaldehyde or acyl); (11) C _1-7 spirocyclyl; (12) thioalkoxy; (13) thiol; (14) -CO ₂ R ^A’ , where R ^A’ is selected from the group consisting of (a) C _1-20 alkyl (e.g., C _1-6 alkyl), (b) C _2-20 alkenyl (e.g., C _2-6 alkenyl), (c) C _6-10 aryl, (d) hydrogen, (e) C _1-6 alk-C _6-10 aryl, (f) amino-C _1-20 alkyl, (g) polyethylene glycol of - (CH2)s2(OCH2CH2)s1(CH2)s3OR’, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R’ is H or C1-20 alkyl, and (h) amino-polyethylene glycol of -NR ^N1 (CH2)s2(CH2CH2O)s1(CH2)s3NR ^N1 , wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R ^N1 is, independently, hydrogen or optionally substituted C _1-6 alkyl; (15) -C(O)NR ^B’ R ^C’ , where each of R ^B’ and R ^C’ is, independently, selected from the group consisting of (a) hydrogen, (b) C _1-6 alkyl, (c) C6-10 aryl, and (d) C1-6 alk-C6-10 aryl; (16) -SO2R ^D’ , where R ^D’ is selected from the group consisting of (a) C1-6 alkyl, (b) C6-10 aryl, (c) C1-6 alk-C6-10 aryl, and (d) hydroxy; (17) - SO2NR ^E’ R ^F’ , where each of R ^E’ and R ^F’ is, independently, selected from the group consisting of (a) hydrogen, (b) C1-6 alkyl, (c) C6-10 aryl and (d) C1-6 alk-C6-10 aryl; (18) -C(O)R ^G’ , where R ^G’ is selected from the group consisting of (a) C _1-20 alkyl (e.g., C _1-6 alkyl), (b) C _2-20 alkenyl (e.g., C _2-6 alkenyl), (c) C _6-10 aryl, (d) hydrogen, (e) C _1-6 alk-C _6-10 aryl, (f) amino-C _1-20 alkyl, (g) polyethylene glycol of -(CH ₂ ) _s2 (OCH ₂ CH ₂ ) _s1 (CH ₂ ) _s3 OR’, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R’ is H or C1-20 alkyl, and (h) amino-polyethylene glycol of -NR ^N1 (CH2)s2(CH2CH2O)s1(CH2)s3NR ^N1 , wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R ^N1 is, independently, hydrogen or optionally substituted C _1-6 alkyl; (19) -NR ^H’ C(O)R ^I’ , wherein R ^H’ is selected from the group consisting of (a1) hydrogen and (b1) C _1-6 alkyl, and R ^I’ is selected from the group consisting of (a2) C _1-20 alkyl (e.g., C _1-6 alkyl), (b2) C _2-20 alkenyl (e.g., C2-6 alkenyl), (c2) C6-10 aryl, (d2) hydrogen, (e2) C1-6 alk-C6-10 aryl, (f2) amino-C1-20 alkyl, (g2) polyethylene glycol of -(CH2)s2(OCH2CH2)s1(CH2)s3OR’, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R’ is H or C1-20 alkyl, and (h2) amino-polyethylene glycol of -NR ^N1 (CH ₂ ) _s2 (CH ₂ CH ₂ O) _s1 (CH ₂ ) _s3 NR ^N1 , wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R ^N1 is, independently, hydrogen or optionally substituted C _1-6 alkyl; (20) - NR ^J’ C(O)OR ^K’ , wherein R ^J’ is selected from the group consisting of (a1) hydrogen and (b1) C1-6 alkyl, and R ^K’ is selected from the group consisting of (a2) C1-20 alkyl (e.g., C1-6 alkyl), (b2) C2-20 alkenyl (e.g., C2-6 alkenyl), (c2) C6-10 aryl, (d2) hydrogen, (e2) C1-6 alk-C6-10 aryl, (f2) amino-C1- 20 alkyl, (g2) polyethylene glycol of -(CH2)s2(OCH2CH2)s1(CH2)s3OR’, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R’ is H or C _1-20 alkyl, and (h2) amino-polyethylene glycol of -NR ^N1 (CH ₂ ) _s2 (CH ₂ CH ₂ O) _s1 (CH ₂ ) _s3 NR ^N1 , wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R ^N1 is, independently, hydrogen or optionally substituted C1-6 alkyl; and (21) amidine. In some embodiments, each of these groups can be further substituted as described herein. [61] The term “aryl,” as used herein, represents a mono-, bicyclic, or multicyclic carbocyclic ring system having one or two aromatic rings and is exemplified by phenyl, naphthyl, 1,2- dihydronaphthyl, 1,2,3,4-tetrahydronaphthyl, anthracenyl, phenanthrenyl, fluorenyl, indanyl, indenyl, and the like, and may be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of: (1) C1-7 acyl (e.g., carboxyaldehyde); (2) C1-20 alkyl (e.g., C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C1-6 alkylsulfinyl-C1-6 alkyl, amino-C1-6 alkyl, azido-C1-6 alkyl, (carboxyaldehyde)-C1-6 alkyl, halo-C1-6 alkyl (e.g., perfluoroalkyl), hydroxy-C1- 6 alkyl, nitro-C1-6 alkyl, or C1-6 thioalkoxy-C1-6 alkyl); (3) C1-20 alkoxy (e.g., C1-6 alkoxy, such as perfluoroalkoxy); (4) C _1-6 alkylsulfinyl; (5) C _6-10 aryl; (6) amino; (7) C _1-6 alk-C _6-10 aryl; (8) azido; (9) C _3-8 cycloalkyl; (10) C _1-6 alk-C _3-8 cycloalkyl; (11) halo; (12) C _1-12 heterocyclyl (e.g., C _1-12 heteroaryl); (13) (C _1-12 heterocyclyl)oxy; (14) hydroxy; (15) nitro; (16) C _1-20 thioalkoxy (e.g., C1-6 thioalkoxy); (17) –(CH2)qCO2R ^A’ , where q is an integer from zero to four, and R ^A’ is selected from the group consisting of (a) C1-6 alkyl, (b) C6-10 aryl, (c) hydrogen, and (d) C1-6 alk- C6-10 aryl; (18) –(CH2)qCONR ^B’ R ^C’ , where q is an integer from zero to four and where R ^B’ and R ^C’ are independently selected from the group consisting of (a) hydrogen, (b) C1-6 alkyl, (c) C6-10 aryl, and (d) C _1-6 alk-C _6-10 aryl; (19) –(CH ₂ ) _q SO ₂ R ^D’ , where q is an integer from zero to four and where R ^D’ is selected from the group consisting of (a) alkyl, (b) C _6-10 aryl, and (c) alk-C _6-10 aryl; (20) –(CH ₂ ) _q SO ₂ NR ^E’ R ^F’ , where q is an integer from zero to four and where each of R ^E’ and R ^F’ is, independently, selected from the group consisting of (a) hydrogen, (b) C _1-6 alkyl, (c) C _6-10 aryl, and (d) C1-6 alk-C6-10 aryl; (21) thiol; (22) C6-10 aryloxy; (23) C3-8 cycloalkoxy; (24) C6-10 aryl-C1-6 alkoxy; (25) C1-6 alk-C1-12 heterocyclyl (e.g., C1-6 alk-C1-12 heteroaryl); (26) C2-20 alkenyl; and (27) C2-20 alkynyl. In some embodiments, each of these groups can be further substituted as described herein. For example, the alkylene group of a C1-alkaryl or a C1- alkheterocyclylcan be further substituted with an oxo group to afford the respective aryloyl and (heterocyclyl)oyl substituent group. [62] The term “acyl,” as used herein, represents an a radical of general formula –C(O)R, where R is an alkyl or aryl group. Examples of an “acyl” group include, but are not limited to, – C(O)CH3, –C(O)C2H5, and –C(O)Ph. [63] The term “carbonyl,” as used herein, represents a C(O) group, which can also be represented as C=O. [64] The term “carboxy,” as used herein, means –CO2H. [65] The term “cycloalkyl,” as used herein represents a monovalent saturated or unsaturated non- aromatic cyclic hydrocarbon group from three to eight carbons, unless otherwise specified, and is exemplified by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicycle heptyl, and the like. When the cycloalkyl group includes one carbon-carbon double bond or one carbon- carbon triple bond, the cycloalkyl group can be referred to as a “cycloalkenyl” or “cycloalkynyl” group respectively. Exemplary cycloalkenyl and cycloalkynyl groups include cyclopentenyl, cyclohexenyl, cyclohexynyl, and the like. Cycloalkyl groups can be optionally substituted with: (1) C1-7 acyl (e.g., carboxyaldehyde); (2) C1-20 alkyl (e.g., C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C1-6 alkylsulfinyl-C _1-6 alkyl, amino-C _1-6 alkyl, azido-C _1-6 alkyl, (carboxyaldehyde)-C _1-6 alkyl, halo- C _1-6 alkyl (e.g., perfluoroalkyl), hydroxy-C _1-6 alkyl, nitro-C _1-6 alkyl, or C _1-6 thioalkoxy-C _1-6 alkyl); (3) C _1-20 alkoxy (e.g., C _1-6 alkoxy, such as perfluoroalkoxy); (4) C _1-6 alkylsulfinyl; (5) C _6- 10 aryl; (6) amino; (7) C1-6 alk-C6-10 aryl; (8) azido; (9) C3-8 cycloalkyl; (10) C1-6 alk-C3-8 cycloalkyl; (11) halo; (12) C1-12 heterocyclyl (e.g., C1-12 heteroaryl); (13) (C1-12 heterocyclyl)oxy; (14) hydroxy; (15) nitro; (16) C1-20 thioalkoxy (e.g., C1-6 thioalkoxy); (17) –(CH2)qCO2R ^A’ , where q is an integer from zero to four, and R ^A’ is selected from the group consisting of (a) C1-6 alkyl, (b) C _6-10 aryl, (c) hydrogen, and (d) C _1-6 alk-C _6-10 aryl; (18) –(CH ₂ ) _q CONR ^B’ R ^C’ , where q is an integer from zero to four and where R ^B’ and R ^C’ are independently selected from the group consisting of (a) hydrogen, (b) C _6-10 alkyl, (c) C _6-10 aryl, and (d) C _1-6 alk-C _6-10 aryl; (19) – (CH ₂ ) _q SO ₂ R ^D’ , where q is an integer from zero to four and where R ^D’ is selected from the group consisting of (a) C6-10 alkyl, (b) C6-10 aryl, and (c) C1-6 alk-C6-10 aryl; (20) –(CH2)qSO2NR ^E’ R ^F’ , where q is an integer from zero to four and where each of R ^E’ and R ^F’ is, independently, selected from the group consisting of (a) hydrogen, (b) C6-10 alkyl, (c) C6-10 aryl, and (d) C1-6 alk-C6-10 aryl; (21) thiol; (22) C6-10 aryloxy; (23) C3-8 cycloalkoxy; (24) C6-10 aryl-C1-6 alkoxy; (25) C1-6 alk-C _1-12 heterocyclyl (e.g., C _1-6 alk-C _1-12 heteroaryl); (26) oxo; (27) C _2-20 alkenyl; and (28) C _2-20 alkynyl. In some embodiments, each of these groups can be further substituted as described herein. For example, the alkylene group of a C ₁ -alkaryl or a C ₁ -alkheterocyclyl can be further substituted with an oxo group to afford the respective aryloyl and (heterocyclyl)oyl substituent group. [66] The term “halogen,” as used herein, represents a halogen selected from bromine, chlorine, iodine, or fluorine. [67] The terms “heteroalkyl” and “heteroalkylidene,” as used herein, each refer to an alkyl group, as defined herein, in which one or two of the constituent carbon atoms have each been replaced by nitrogen, oxygen, or sulfur. In some embodiments, the heteroalkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for alkyl groups. The terms “heteroalkenyl” and heteroalkynyl,” as used herein refer to alkenyl and alkynyl groups, as defined herein, respectively, in which one or two of the constituent carbon atoms have each been replaced by nitrogen, oxygen, or sulfur. In some embodiments, the heteroalkenyl and heteroalkynyl groups can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for alkyl groups. [68] The term “heteroaryl,” as used herein, represents that subset of heterocyclyls, as defined herein, which are aromatic: i.e., they contain 4n+2 pi electrons within the mono- or multicyclic ring system. Exemplary unsubstituted heteroaryl groups are of 1 to 12 (e.g., 1 to 11, 1 to 10, 1 to 9, 2 to 12, 2 to 11, 2 to 10, or 2 to 9) carbons. In some embodiment, the heteroaryl is substituted with 1, 2, 3, or 4 substituents groups as defined for a heterocyclyl group. [69] The term “oxo” as used herein, represents =O. [70] The term “polyethylene glycol,” as used herein, represents an alkoxy chain comprised of one or more monomer units, each monomer unit consisting of –OCH ₂ CH ₂ -. Polyethyelene glycol (PEG) is also sometimes referred to as polyethylene oxide (PEO) or polyoxyethylene (POE), and these terms may be considered interchangeable for the purpose of this disclosure. For example, a polyethylene glycol may have the structure, -(CH ₂ ) _s2 (OCH ₂ CH ₂ ) _s1 (CH ₂ ) _s3 O-, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), and each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10). Polyethylene glycol may also be considered to include an amino-polyethylene glycol of - NR ^N1 (CH2)s2(CH2CH2O)s1(CH2)s3NR ^N1 -, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R ^N1 is, independently, hydrogen or optionally substituted C _1-6 alkyl. [71] The term “isomer,” as used herein, means any tautomer, stereoisomer, enantiomer, or diastereomer of any compound. It is recognized that the compounds can have one or more chiral centers and/or double bonds and, therefore, exist as stereoisomers, such as double-bond isomers (i.e., geometric E/Z isomers) or diastereomers, enantiomers (i.e., (+) or (-)) or cis/trans isomers). Unless otherwise noted, chemical structures depicted herein encompass all of the corresponding stereoisomers, that is, both the stereomerically pure form (e.g., geometrically pure, enantiomerically pure, or diastereomerically pure) and enantiomeric and stereoisomeric mixtures, e.g., racemates. Enantiomeric and stereoisomeric mixtures of compounds can typically be resolved into their component enantiomers or stereoisomers by well-known methods, such as chiral-phase gas chromatography, chiral-phase high performance liquid chromatography, crystallizing the compound as a chiral salt complex, or crystallizing the compound in a chiral solvent. Enantiomers and stereoisomers can also be obtained from stereomerically or enantiomerically pure intermediates, reagents, and catalysts by well-known asymmetric synthetic methods. [72] The term “stereoisomer,” as used herein, refers to all possible different isomeric as well as conformational forms which a compound may possess (e.g., a compound of any formula described herein), in particular all possible stereochemically and conformationally isomeric forms, all diastereomers, enantiomers and/or conformers of the basic molecular structure. Some compounds may exist in different tautomeric forms, all of the latter being included within the scope of the present disclosure. [73] The term “diastereomer,” as used herein means stereoisomers that are not mirror images of one another and are non-superimposable on one another. [74] The term “enantiomer,” as used herein, means each individual optically active form of a compound, having an optical purity or enantiomeric excess (as determined by methods standard in the art) of at least 80% (i.e., at least 90% of one enantiomer and at most 10% of the other enantiomer), preferably at least 90% and more preferably at least 98%. Other terms [75] As used herein, the term “about” or “approximately” refers to a ±10% variation from the recited quantitative value (and includes the recited quantitative value itself) unless otherwise indicated or inferred from the context. For example, unless otherwise stated or inferred from the context, a dose of about 100 kBq/kg indicates a dose range of 100±10% kBq/kg, i.e., from 90 kBq/kg to 110 kBq/kg, inclusive. [76] As used herein, the term “administered in combination,” “combined administration,” or “co- administered” means that two or more agents are administered to a subject at the same time or within an interval such that there may be an overlap of an effect of each agent on the patient. Thus, two or more agents that are administered in combination need not be administered together. In some embodiments, they are administered within 90 days (e.g., within 80, 70, 60, 50, 40, 30, 20, 10, 5, 4, 3, 2, or 1 day(s)), within 28 days (e.g., with 14, 7, 6, 5, 4, 3, 2, or 1 day(s), within 24 hours (e.g., 12, 6, 5, 4, 3, 2, or 1 hour(s), or within about 60, 30, 15, 10, 5, or 1 minute of one another. In some embodiments, the administrations of the agents are spaced sufficiently closely together such that a combinatorial effect is achieved. [77] As used herein, “administering” an agent to a subject includes contacting cells of said subject with the agent. [78] The term “cancer” refers to any cancer caused by the proliferation of malignant neoplastic cells, such as tumors, neoplasms, carcinomas, sarcomas, leukemias, and lymphomas. A “solid tumor cancer” is a cancer comprising an abnormal mass of tissue, e.g., sarcomas, carcinomas, and lymphomas. A “hematological cancer” or “liquid cancer,” as used interchangeably herein, is a cancer present in a body fluid, e.g., lymphomas and leukemias. [79] The term “chelate” as used herein, refers to an organic compound or portion thereof that can be bonded to a central metal or radiometal atom at two or more points. [80] The term “conjugate,” as used herein, refers to a molecule that contains a chelating group or metal complex thereof, a linker group, and which optionally contains a therapeutic moiety or a targeting moiety. [81] The term “therapeutic moiety” as used herein refers to any molecule or any part of a molecule that confers a therapeutic benefit. In some embodiments, the therapeutic moiety is a protein or polypeptide, e.g., an antibody, an antigen-binding fragment thereof. In some embodiments, the therapeutic moiety is a small molecule. [82] The term “targeting moiety” as used herein refers to any molecule or any part of a molecule that binds to a given target. In some embodiments, the targeting moiety is a protein or polypeptide such as an antibody or antigen binding fragment thereof, a nanobody, an affibody, or a consensus sequence from a Fibronectin type III domain. In some embodiments, the targeting moiety is a peptide or a small molecule. [83] As used herein, the term “compound,” is meant to include all stereoisomers, geometric isomers, and tautomers of the structures depicted. [84] The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present disclosure that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically active starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present disclosure. Cis and trans geometric isomers of the compounds of the present disclosure are described and may be isolated as a mixture of isomers or as separated isomeric forms. [85] Compounds of the present disclosure also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond and the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Examples prototropic tautomers include ketone – enol pairs, amide – imidic acid pairs, lactam – lactim pairs, amide – imidic acid pairs, enamine – imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, such as, 1H- and 3H-imidazole, 1H-, 2H- and 4H- 1,2,4- triazole, 1H- and 2H- isoindole, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. [86] At various places in the present specification, substituents of compounds of the present disclosure are disclosed in groups or in ranges. It is specifically intended that the present disclosure include each and every individual sub-combination of the members of such groups and ranges. For example, the term “C1-6 alkyl” is specifically intended to individually disclose methyl, ethyl, C ₃ alkyl, C ₄ alkyl, C ₅ alkyl, and C ₆ alkyl. Herein a phrase of the form “optionally substituted X” (e.g., optionally substituted alkyl) is intended to be equivalent to “X, wherein X is optionally substituted” (e.g., “alkyl, wherein said alkyl is optionally substituted”). It is not intended to mean that the feature “X” (e.g., alkyl) per se is optional. [87] As used herein, the terms “decrease,” “decreased,” “increase,” “increased,” or “reduction,” “reduced,” (e.g., in reference to therapeutic outcomes or effects) have meanings relative to a reference level. In some embodiments, the reference level is a level as determined by the use of said method with a control in an experimental animal model or clinical trial. In some embodiments, the reference level is a level in the same subject before or at the beginning of treatment. In some embodiments, the reference level is the average level in a population not being treated by said method of treatment. [88] The term an “effective amount” of an agent (e.g., any of the foregoing compounds or conjugates), as used herein, is that amount sufficient to effect beneficial or desired results, such as clinical results, and, as such, an “effective amount” depends upon the context in which it is being applied. [89] The term “pharmaceutical composition,” as used herein, represents a composition containing a compound described herein formulated with a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition is manufactured or sold with the approval of a governmental regulatory agency as part of a therapeutic regimen for the treatment of disease in a mammal. Pharmaceutical compositions can be formulated, for example, for oral administration in unit dosage form (e.g., a tablet, capsule, caplet, gelcap, or syrup); for topical administration (e.g., as a cream, gel, lotion, or ointment); for intravenous administration (e.g., as a sterile solution free of particulate emboli and in a solvent system suitable for intravenous use); or in any other formulation described herein. [90] A “pharmaceutically acceptable excipient,” as used herein, refers any ingredient other than the compounds described herein (for example, a vehicle capable of suspending or dissolving the active compound) and having the properties of being nontoxic and non-inflammatory in a patient. Excipients may include, for example: antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes (colors), emollients, emulsifiers, fillers (diluents), film formers or coatings, flavors, fragrances, glidants (flow enhancers), lubricants, preservatives, printing inks, radioprotectants, sorbents, suspending or dispersing agents, sweeteners, or waters of hydration. Exemplary excipients include, but are not limited to: ascorbic acid, histidine, phosphate buffer, butylated hydroxytoluene (BHT), calcium carbonate, calcium phosphate (dibasic), calcium stearate, croscarmellose, crosslinked polyvinyl pyrrolidone, citric acid, crospovidone, cysteine, ethylcellulose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, maltitol, mannitol, methionine, methylcellulose, methyl paraben, microcrystalline cellulose, polyethylene glycol, polyvinyl pyrrolidone, povidone, pregelatinized starch, propyl paraben, retinyl palmitate, shellac, silicon dioxide, sodium carboxymethyl cellulose, sodium citrate, sodium starch glycolate, sorbitol, starch (corn), stearic acid, stearic acid, sucrose, talc, titanium dioxide, vitamin A, vitamin E, vitamin C, and xylitol. [91] The term “pharmaceutically acceptable salt,” as use herein, represents those salts of the compounds described here that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and animals without undue toxicity, irritation, or allergic response. Pharmaceutically acceptable salts are well known in the art. For example, pharmaceutically acceptable salts are described in: Berge et al., J. Pharmaceutical Sciences 66:1-19, 1977 and in Pharmaceutical Salts: Properties, Selection, and Use, (Eds. P.H. Stahl and C.G. Wermuth), Wiley-VCH, 2008. The salts can be prepared in situ during the final isolation and purification of the compounds described herein or separately by reacting the free base group with a suitable organic acid. [92] Compounds may have ionizable groups so as to be capable of preparation as pharmaceutically acceptable salts. These salts may be acid addition salts involving inorganic or organic acids or the salts may, in the case of acidic forms of compounds, be prepared from inorganic or organic bases. Frequently, the compounds are prepared or used as pharmaceutically acceptable salts prepared as addition products of pharmaceutically acceptable acids or bases. Suitable pharmaceutically acceptable acids and bases are well-known in the art, such as hydrochloric, sulphuric, hydrobromic, acetic, lactic, citric, or tartaric acids for forming acid addition salts, and potassium hydroxide, sodium hydroxide, ammonium hydroxide, caffeine, various amines for forming basic salts. Methods for preparation of the appropriate salts are well- established in the art. [93] Representative acid addition salts include acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, valerate salts, among others. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, and magnesium, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, and ethylamine. [94] The term “radiopharmaceutical” or “radioconjugate,” as used herein, refers to any compound or conjugate that includes a radioisotope or radionuclide, such as any of the radioisotopes or radionuclides described herein. [95] As used herein, the term “radionuclide,” refers to an atom capable of undergoing radioactive decay (e.g., ³ H, ¹⁴ C, ¹⁵ N, ¹⁸ F, ³⁵ S, ⁴⁷ Sc, ⁵⁵ Co, ⁶⁰ Cu, ⁶¹ Cu, ⁶² Cu, ⁶⁴ Cu, ⁶⁷ Cu, ⁷⁵ Br, ⁷⁶ Br , ⁷⁷ Br , ⁸⁹ Zr, ⁸⁶ Y, ⁸⁷ Y, ⁹⁰ Y, ⁹⁷ Ru, ⁹⁹ Tc, ^99m Tc, ¹⁰⁵ Rh, ¹⁰⁹ Pd, ¹¹¹ In, ¹²³ I, ¹²⁴ I, ¹²⁵ I, ¹³¹ I, ¹⁴⁹ Pm, ¹⁴⁹ Tb, ¹⁵³ Sm, ¹⁶⁶ Ho, ¹⁷⁷ Lu, ¹⁸⁶ Re, ¹⁸⁸ Re, ¹⁹⁸ Au, ¹⁹⁹ Au, ²⁰³ Pb, ²¹¹ At, ²¹² Pb , ²¹² Bi, ²¹³ Bi, ²²³ Ra, ²²⁵ Ac, ²²⁷ Th, ^229Th , ⁶⁶ Ga, ⁶⁷ Ga, ⁶⁸ Ga, ⁸² Rb, ^117m Sn, or ²⁰¹ Tl). The terms radioactive nuclide, radioisotope, or radioactive isotope may also be used to describe a radionuclide. Radionuclides may be used as detection agents. Exemplary radionuclides used in this disclosure include, but are not limited to, ⁴³ Sc, ⁴⁴ Sc, ⁴⁷ Sc, ⁵⁵ Co, ⁶⁰ Cu, ⁶¹ Cu, ⁶² Cu, ⁶⁴ Cu, ⁶⁷ Cu, ⁶⁶ Ga, ⁶⁷ Ga, ⁶⁸ Ga, ⁸² Rb, ⁸⁶ Y, ⁸⁷ Y, ⁸⁹ Zr, ⁹⁰ Y, ⁹⁷ Ru, ⁹⁹ Tc, ^99m Tc, ¹⁰⁵ Rh, ¹⁰⁹ Pd, ¹¹¹ In, ^117m Sn, ¹³³ La, ¹³⁴ Ce, ¹⁴⁹ Pm, ¹⁴⁹ Tb, ¹⁵³ Sm, ¹⁵² Tb, ¹⁵⁵ Tb, ¹⁶¹ Tb, ¹⁶⁶ Ho, ¹⁷⁷ Lu, ¹⁸⁶ Re, ¹⁸⁸ Re, ¹⁹⁸ Au, ¹⁹⁹ Au, ²⁰¹ Tl, ²⁰³ Pb, ²¹¹ At, ²¹² Pb, ²¹² Bi, ²¹³ Bi, ²²³ Ra, ²²⁵ Ac, ²²⁷ Th, and ²²⁹ Th. [96] As used herein, and as well understood in the art, “to treat” a condition or “treatment” of the condition (e.g., the conditions described herein such as cancer) is an approach for obtaining beneficial or desired results, such as clinical results. Beneficial or desired results can include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions; diminishment of extent of disease, disorder, or condition; stabilized (i.e., not worsening) state of disease, disorder, or condition; preventing spread of disease, disorder, or condition; delay or slowing the progress of the disease, disorder, or condition; amelioration or palliation of the disease, disorder, or condition; and remission (whether partial or total), whether detectable or undetectable. In the context of cancer treatment, “ameliorating” may include, for example, reducing incidence of metastases, reducing tumor volume, reducing tumor vascularization and/or reducing the rate of tumor growth. “Palliating” a disease, disorder, or condition means that the extent and/or undesirable clinical manifestations of the disease, disorder, or condition are lessened and/or time course of the progression is slowed or lengthened, as compared to the extent or time course in the absence of treatment. Compounds [97] The disclosure is directed to, in part, compounds that are radiopharmaceuticals. In some embodiments, a disclosed compound is selected from the group consisting of the compounds identified in Table 1. Table 1. Compound Structure Compound A HO ₂ C H ^O _2C N N O O O O N N N O O N CO ₂ H H CO ₂ H HO HN N O N N OH Compound B ^CO ₂ ^{H N} _N ^CO ₂ ^H O O O O N N N O O N 3 H H ^O ₂ ^C HO HN N O N N OH Compound C ^CO ₂ ^{H N} _N CO ₂ ^H O O O O N N N O O N 9 H H ^O ₂ ^C HO HN N O OH N N Compound D O CO H ₂ H O O N COH N N O O N N ₂ H O N ^N HO ₂ C HO ₂ C HO HN N O OH N N Compound E _HO ^O O HO ^N _N O H H O O N N _{N N} ^OH N O O N H O O O ^OH HO O N N N H O ^H N Compound F _HO ^O O OH HO ^N _N O O O H O N _{N N} ^OH N O O N H O O O ^OH HO O N N O ^H N N H Compound G O ^O _OH H O N N ^{N N} _OH O HO _N ^N O H ^O _O HO O N N N N H O ^H Compound H O N O OH H N O N N O OH HO O HO N N HO O O N HO N O N N H OH Compound I O ^HO O OH _O HO ^N _N O H ^O N N ^OH N N _N H O O O OH HO O N N N N H OH Compound J HO O O HO O O H H N N N N N N H OH O O N N O H ₂ N O HN OH HO O H ₂ N NH O N N N H OH N Compound K O OH O H O N N N ^N H _N OH O HO N ^N O H ^O _O HO O N N N N H OH Compound L O OH N O N O N N OH N HO O HO O N N N N H O ^H Compound M _HO ^O O HO ^N _N O N _N ^OH N O O OH HO O N N H OH N N Compound N _HO ^O O HO ^N _N O N _N ^OH N O O ^OH BnO O N N N N H OBn Chelators [98] The compounds of Formula I comprise chelating moieties or chelators. [99] As disclosed herein, the chelator can be selected from the group consisting of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), DOTMA (1R,4R,7R,10R)-Į^^Į¶^^Į´^^ Į¶´-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-t etraacetic acid, DOTAM (1,4,7,10- tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane), DOTPA (1,4,7,10- tetraazacyclododecane-1,4,7,10-tetra propionic acid), DO3AM-acetic acid (2-(4,7,10-tris(2- amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetic acid), DOTA-GA anhydride (2,2’,2”-(10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,1 0-tetraazacyclododecane-1,4,7- triyl)triacetic acid, DOTP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid)), DOTMP (1,4,6,10-tetraazacyclodecane-1,4,7,10-tetramethylene phosphonic acid, DOTA- 4AMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(acetamido- methylenephosphonic acid), CB-TE2A (1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4,11-diacetic acid), NOTA (1,4,7- triazacyclononane-1,4,7-triacetic acid), NODA-GA (1,4,7-triazacyclononane-4,7-diacetic acid-1- [2-glutaric acid]), NOTP (1,4,7-triazacyclononane-1,4,7-tri(methylene phosphonic acid), TETPA (1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrapropionic acid), TETA (1,4,8,11- tetraazacyclotetradecane-1,4,8,11-tetra acetic acid), HEHA (1,4,7,10,13,16- hexaazacyclohexadecane-1,4,7,10,13,16-hexaacetic acid), PEPA (1,4,7,10,13- pentaazacyclopentadecane-N,N’,N”,N’’’, N’’’’-pentaacetic acid), H ₄ octapa (N,N’-bis(6-carboxy- 2-pyridylmethyl)-ethylenediamine-N,N’-diacetic acid), H ₂ dedpa (1,2-[[6-(carboxy)-pyridin-2- yl]-methylamino]ethane), H ₆ phospa (N,N’-(methylenephosphonate)-N,N’-[6- (methoxycarbonyl)pyridin-2-yl]-methyl-1,2-diaminoethane), TTHA (triethylenetetramine- N,N,N’,N”,N’’’, N’’’-hexaacetic acid), DO2P (tetraazacyclododecane dimethanephosphonic acid), HP-DO3A (hydroxypropyltetraazacyclododecanetriacetic acid), EDTA (ethylenediaminetetraacetic acid), Deferoxamine, DTPA (diethylenetriaminepentaacetic acid), DTPA-BMA (diethylenetriaminepentaacetic acid-bismethylamide), and porphyrin. [100] In certain embodiments, the chelator is selected from DOTA, DOTA-GA, NOTA, NODA-GA, NODA-SA, DTPA, TETA, EDTA, TRITA, CDTA, and DFO, which are defined as below: DOTA stands for 1,4,7,10-tetrazacyclododecane-1,4,7,10-tetraacetic acid, DOTA-GA, or DOTAGA as used herein, stands for 1,4,7,10-tetraazacyclododececane,1- (glutaric acid)-4,7,10-triacetic acid, NOTA stands for 1,4,7-triazacyclononanetriacetic acid, NODA-GA, or NODAGA as used herein, stands for 1,4,7-triazacyclononane-N-glutaric acid-N',N"-diacetic acid, NODA-SA stands for 1,4,7- triazacyclononane -1-succinic acid-4,7-diacetic acid, DTPA stands for diethylenetriaminepentaacetic acid, TETA stands for 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid, EDTA stands for ethylenediamine-N,N'-tetraacetic acid, TRITA stands for 1,4,7,10 tetraazacyclotridecane-l,4,7,10-tetraacetic acid, CDTA stands for trans-1,2-diaminocyclohexane-1^1^1ƍ^1ƍ-tetraacetic acid, DFO stands for the Desferal or Desferrioxamine type group of chelators, the chemical name of the non-limiting example is N-[5-({3-[5-(Acetyl-hydroxy-amino)-pentylcarbamoyl]- propionyl}-hydroxy-amino)-pentyl]-N'-(5-amino-pentyl)-N'-hyd roxy-succinamide, and with the chemical structures thereof being as follows: O HO O N N HO O OH N N HO O O OH DOTA-GA CO ₂ H _CO2 ^H N COH N N _{2 HO2C} N CO ₂ H N N CO HO ₂ C HO ₂ H 2C N N COH HO _{2 2} C EDTA NODA-GA NODA-SA COH CO ₂ H ₂ [101] In certain embodiments, the chelator is selected from DOTA, DOTAGA, NOTA, and NODAGA. [102] In certain embodiments, the chelator is DOTAGA and the compounds have the structure of Formula II:

O HO O N N HO O Z ¹ OH X N N N Y Z ² n O O ^OH HO HN N O N N OH (II), wherein each of variables X, Y, n, Z ¹ , and Z ² is as defined in the SUMMARY section above. [103] In certain embodiments, the chelator is represented by the variable W. In some O HO O N N HO O OH N N embodiments, W is selected from the group consisting of O , O HO O OH OH N N O HO O O N OH N N N N N O N N O O ^OH , ^O _O ^OH , and ^{O OH} _O ^OH . Radionuclides [104] The present disclosure includes radiopharmaceuticals each comprising a radionuclide. Examples of suitable radionuclides include, but are not limited to, ⁴³ Sc, ⁴⁴ Sc, ⁴⁷ Sc, ⁵⁵ Co, ⁶⁰ Cu, ⁶¹ Cu, ⁶² Cu, ⁶⁴ Cu, ⁶⁷ Cu, ⁶⁶ Ga, ⁶⁷ Ga, ⁶⁸ Ga, ⁸² Rb, ⁸⁶ Y, ⁸⁷ Y, ⁸⁹ Zr, ⁹⁰ Y, ⁹⁷ Ru, ⁹⁹ Tc, ^99m Tc, ¹⁰⁵ Rh, ¹⁰⁹ Pd, ¹¹¹ In, ^117m Sn, ¹³³ La, ¹³⁴ Ce, ¹⁴⁹ Pm, ¹⁴⁹ Tb, ¹⁵³ Sm, ¹⁵² Tb, ¹⁵⁵ Tb, ¹⁶¹ Tb, ¹⁶⁶ Ho, ¹⁷⁷ Lu, ¹⁸⁶ Re, ¹⁸⁸ Re, ¹⁹⁸ Au, ¹⁹⁹ Au, ²⁰¹ Tl, ²⁰³ Pb, ²¹¹ At, ²¹² Pb, ²¹² Bi, ²¹³ Bi, ²²³ Ra, ²²⁵ Ac, ²²⁷ Th, and ²²⁹ Th. [105] In some embodiments, the radionuclide is selected from the group consisting of ⁶⁴ Cu, ⁶⁷ Cu, ⁶⁸ Ga, ⁹⁰ Y, ¹¹¹ In, ¹⁴⁹ Tb, ¹⁵³ Sm, ¹⁷⁷ Lu, ²¹¹ At, ²¹² Bi, ²¹² Pb, ²¹³ Bi, ²²³ Ra, ²²⁵ Ac, and ²²⁷ Th. [106] In some embodiments, the radionuclide is ⁶⁸ Ga, ⁸⁹ Zr, ⁹⁰ Y, ¹¹¹ In, ¹⁷⁷ Lu, or ²²⁵ Ac. In certain embodiments, the radionuclide is ¹⁷⁷ Lu or ²²⁵ Ac. [107] In some embodiments, the radionuclide used herein is a beta-emitting radionuclide such as ¹⁷⁷ Lu. In some embodiments, the radionuclide used herein is an alpha-emitting radionuclide such as ²²⁵ Ac. Linkers [108] The compounds of the present disclosure comprise the unique linker as shown within the Z ¹ X Y ^{2 n Z} structure of Formula I that comprises , wherein X is absent or C=O; Y is each independently O or NR, R being H, alkyl, aryl, or acyl; n is an integer of 0-5 (inclusive); Z ¹ and Z ² each are, independently, absent or an amino acid unit. [109] The term “amino acid unit” described herein refers to one or more organic moieties each formed from an amino acid (e.g., a natural amino acid or an unnatural amino acid). Typically, an amino acid unit is formed as shown below: O ^O _H N NH HO ₂ 2 ² R R a _{mino acid} ^{amino acid unit} where R ² represents an alkyl, cycloalkyl, aryl, or heteroaryl, each of which can be optionally substituted with a suitable substituent described herein (e.g., -C(O)OH, -NH ₂ , -NH ₃ +, - NH(CNH2 ⁺ )NH2); alternatively, R ² together with the -NH2 group within the amino acid form a heterocycle. [110] In some embodiments, an amino acid unit refers to an organic moiety formed from aspartic acid (Asp), glutamic acid (Glu), 2,4-diaminobutyric acid (Dab), 2,3-diaminopropionic acid (Dap), lysine (Lys), or arginine (Arg), with their structures shown below:

NH ₂ H ₂ N COOH H ₂ N COOH 2,4-diaminobutyric acid (Dab) Glycine (Gly, G) NH ₂ H ₂ N COOH 2,3-diaminopropionic acid (Dap) [111] In some embodiments, the compounds of Formula I or Formula II feature that the amino acid unit comprises an organic moiety formed from aspartic acid (Asp), for example, with the OH O N H structure shown as (including its stereoisomers) O . [112] In some embodiments, the compounds of Formula I or Formula II feature that the amino O H N acid unit is formed from glycine (Gly), for example, with the structure . [113] In some embodiments, the compounds of Formula I or Formula II feature that the amino acid unit is formed from glutamic acid (Glu), for example, with the structure shown below O H N (including its stereoisomers) HO O . [114] In some embodiments, an amino acid unit refers to a fragment comprising multiple organic moieties formed from glutamine, glutamic acid, and arginine, with their structures shown below, including all their stereoisomers: HO O HO O HO O O O O O H H H H N N N N N N N H H H O O O H H ₂ N O HN H ^N _O N 2 H ₂ N NH H ₂ N NH . [115] In some embodiments, the compounds of Formula I or Formula II feature that X is C=O. [116] In some embodiments, the compounds of Formula I or Formula II feature that n is 1, 2, 3, 4, or 5. In certain embodiments, n is 4 or 5. [117] In some embodiments, the compounds of Formula I or Formula II feature that each of Z ¹ and Z ² is absent. [118] In some embodiments, the compounds of Formula I or Formula II feature that each of Z ¹ and Z ² is absent, X is C=O, Y is each independently O or NH, and n is 0, 1, 2, 3, 4, or 5. Exemplary linkers include, but are not limited to, the following: O O O H O N O N , , O O N H , ^H , O O H O N O ^O O O O _{O N} , and ^H , each of which can be optionally substituted with a suitable substituent described herein. [119] In some embodiments, the compounds of Formula I or Formula II feature that X is C=O, n is 4 or 5, Z ¹ is an amino acid unit, and Z ² is absent. A representative exemplary compound is one of the following: O HO O N N HO O H O OH (S) N O O N N N O N H O O CO ₂ ^H O OH HO HN N O N N OH , and O HO O N N HO O H O OH (S) N O O N N N O N H O O C ^O ₂ ^H HO HN N O OH N N . [120] In some embodiments, the compounds of Formula I or Formula II feature that X is C=O, n is 4 or 5, Z ¹ is absent, and Z ² is an amino acid unit. A representative exemplary compound is one of the following: O HO O N N H ^O HO O _2C O H OH O N N N N O O _(S) ^N H O O O OH HO HN N O N N OH , and

O HO O N N H ^O HO O ₂ ^C O H OH O N N N N O O (S) N H O O HO HN N O N N OH . [121] In some embodiments, the compounds of Formula I or Formula II feature that X is (C=O)NH, n is 4 or 5, each of Z ¹ and Z ² is absent. A representative exemplary compound is one of the following: O OH O H O N O N N _O ^O O N N H O OH HO N N O HO O HO HN N O OH N N , and O H O N O N N _O ^O O H O ^{N N} O _H HO N N O HO O HO HN N O OH N N . [122] In some embodiments, the compounds of Formula I or Formula II feature that X is C=O, n is 4 or 5, Z ¹ is absent, and Z ² is (C=O)NH(CH ₂ CH ₂ )NH. A representative exemplary compound is one of the following: HO O O N N HO O H H O OH O N N N N N ^O _O N O H O O ^OH HO HN N O OH N N , and HO O O N N HO O H H O OH O N N O N N N ^O N O H O HO HN N O N N OH . [123] In some embodiments, the compounds of Formula I or Formula II feature that X is absent, n is 0, Z ¹ is absent, and Z ² is an amino acid unit. Thus, the linker of such compounds O _H N would be: ^R2 , wherein R ² represents an alkyl, cycloalkyl, aryl, or heteroaryl, each of which can be optionally substituted with a suitable substituent described herein; alternatively, R ² together with the -NH2 group within the amino acid form a heterocycle. [124] A representative exemplary compound is one of the following: O ^O _OH H O (S) N N N N O OH C _O2 ^H HO N N O HO O HO HN N O N N OH , and O O H N OH (S) N N N O N CO H HO N 2 HO O O HO HN N O N N OH . [125] In some embodiments, the compounds of Formula I or Formula II feature that X is absent, n is 0, each of Z ¹ and Z ² is absent. A representative exemplary compound is one of the following: O O HO HO O O N N N N HO HO O OH O OH N N N N N O N O O ^OH HO HN HO HN N N O O N N N N OH , and OH . Subjects [126] In some disclosed methods, a therapy (e.g., comprising a therapeutic agent) is administered to a subject. In some embodiments, the subject is a mammal, e.g., a human. [127] In some embodiments, the subject has cancer or is at risk of developing cancer. For example, the subject may have been diagnosed with cancer. The cancer may be a primary cancer or a metastatic cancer. Subjects may have any stage of cancer, e.g., stage I, stage II, stage III, or stage IV with or without lymph node involvement and with or without metastases. Provided compositions may prevent or reduce further growth of the cancer and/or otherwise ameliorate the cancer (e.g., prevent or reduce metastases). In some embodiments, the subject does not have cancer but has been determined to be at risk of developing cancer, e.g., because of the presence of one or more risk factors such as environmental exposure, presence of one or more genetic mutations or variants, family history, etc. In some embodiments, the subject has not been diagnosed with cancer. [128] In some embodiments, the cancer is small-cell lung cancer, non-small-cell lung cancer, sarcoma, pancreatic cancer, breast cancer, or colon cancer. Administration and dosage Effective doses [129] The present disclosure provides methods of using a compound of Formula I for treating clinical indications expressing HSP90, with the compound administered to a subject (e.g., a human) in an amount therapeutically effective for such treatment. [130] This disclosure also covers combination therapies in which the amounts of each therapeutic may or may not be, on their own, therapeutically effective. In some embodiments, therapeutic combinations as disclosed herein are administered to a subject in a manner (e.g., dosing amount and timing) sufficient to cure or at least partially arrest the symptoms of the disorder and its complications. In the context of a single therapy (a “monotherapy”), an amount adequate to accomplish this purpose is defined as a “therapeutically effective amount,” an amount of a compound sufficient to substantially improve at least one symptom associated with the disease or a medical condition. The “therapeutically effective amount” typically varies depending on the therapeutic. For known therapeutic agents, the relevant therapeutically effective amounts may be known to or readily determined by those of skill in the art. [131] For example, in the treatment of cancer, an agent or compound that decreases, prevents, delays, suppresses, or arrests any symptom of the disease or condition would be therapeutically effective. A therapeutically effective amount of an agent or compound is not required to cure a disease or condition but will provide a treatment for a disease or condition such that the onset of the disease or condition is delayed, hindered, or prevented, or the disease or condition symptoms are ameliorated, or the term of the disease or condition is changed or, for example, is less severe or recovery is accelerated in an individual. For example, a treatment may be therapeutically effective if it causes a cancer to regress or to slow the cancer’s growth. [132] The dosage regimen (e.g., amounts of each therapeutic, relative timing of therapies, etc.) that is effective for these uses may depend on the severity of the disease or condition and the weight and general state of the subject. For example, the therapeutically effective amount of a particular composition comprising a therapeutic agent applied to mammals (e.g., humans) can be determined by the person of ordinary skill in the art with consideration of individual differences in age, weight, and the condition of the mammal. Because certain conjugates of the present disclosure exhibit an enhanced ability to target cancer cells and residualize, the dosage of these compounds can be lower than (e.g., less than or equal to about 90%, 75%, 50%, 40%, 30%, 20%, 15%, 12%, 10%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1% of) the equivalent dose of required for a therapeutic effect of the unconjugated agent. Therapeutically effective and/or optimal amounts can also be determined empirically by those of skill in the art. Thus, lower effective doses can also be determined by those of skill in the art. [133] Single or multiple administrations of a radiopharmaceutical or a composition (e.g., a pharmaceutical composition comprising a therapeutic agent or a radiopharmaceutical) can be carried out with dose levels and pattern being selected by the treating physician. The dose and administration schedule can be determined and adjusted based on the severity of the disease or condition in the subject, which may be monitored throughout the course of treatment according to the methods commonly practiced by clinicians or those described herein. [134] As provided above, a radiopharmaceutical compound of this disclosure may be administered in combination with another therapeutic agent. In the disclosed combination therapy methods, the first and second therapies may be administered sequentially or concurrently to a subject. For example, a first composition comprising a first therapeutic agent and a second composition comprising a second therapeutic agent may be administered sequentially or concurrently to a subject. Alternatively, a composition comprising a combination of a first therapeutic agent and a second therapeutic agent may be administered to the subject. [135] In some embodiments, the radiopharmaceutical is administered in a single dose. In some embodiments, the radiopharmaceutical is administered more than once, i.e., multiple doses. When the radiopharmaceutical is administered more than once, the dose of each administration may be the same or different. [136] In some embodiments, compositions (such as compositions comprising radiopharmaceuticals) are administered for radiation treatment planning or diagnostic purposes. When administered for radiation treatment planning or diagnostic purposes, compositions may be administered to a subject in a diagnostically effective dose and/or an amount effective to determine the therapeutically effective dose. In some embodiments, a first dose of disclosed conjugate or a composition (e.g., pharmaceutical composition) thereof is administered in an amount effective for radiation treatment planning, followed administration of a combination therapy including a conjugate as disclosed herein and another therapeutic. [137] Pharmaceutical compositions comprising one or more agents (e.g., radiopharmaceuticals) can be formulated for use in accordance with disclosed methods and systems in a variety of drug delivery systems. One or more physiologically acceptable excipients or carriers can also be included in the composition for proper formulation. Examples of suitable formulations are found in Remington’s Pharmaceutical Sciences, Mack Publishing Company, Philadelphia, PA, 17th ed., 1985. For a brief review of methods for drug delivery, see, e.g., Langer (Science 249:1527- 1533, 1990). Formulations [138] Pharmaceutical compositions may be formulated for parenteral, intranasal, topical, oral, or local administration, such as by a transdermal means, for prophylactic and/or therapeutic treatment. Pharmaceutical compositions can be administered parenterally (e.g., by intravenous, intramuscular, or subcutaneous injection), or by oral ingestion, or by topical application or intraarticular injection at areas affected by the vascular or cancer condition. Examples of additional routes of administration include intravascular, intra-arterial, intratumor, intraperitoneal, intraventricular, intraepidural, as well as nasal, ophthalmic, intrascleral, intraorbital, rectal, topical, or aerosol inhalation administration. Also specifically contemplated are sustained release administration, by such means as depot injections or erodible implants or components. Suitable compositions include compositions comprising include agents (e.g., compounds as disclosed herein) dissolved or suspended in an acceptable carrier, preferably an aqueous carrier, e.g., water, buffered water, saline, or PBS, among others, e.g., for parenteral administration. Compositions may contain pharmaceutically acceptable auxiliary substances to approximate physiological conditions, such as pH adjusting and buffering agents, tonicity adjusting agents, wetting agents, or detergents, among others. In some embodiments, compositions are formulated for oral delivery; for example, compositions may contain inert ingredients such as binders or fillers for the formulation of a unit dosage form, such as a tablet or a capsule. In some embodiments, compositions are formulated for local administration; for example, compositions may contain inert ingredients such as solvents or emulsifiers for the formulation of a cream, an ointment, a gel, a paste, or an eye drop. [139] Compositions may be sterilized, e.g., by conventional sterilization techniques, or sterile filtered. Aqueous solutions may be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous carrier prior to administration. The pH of the preparations typically will be between 3 and 11, more preferably between 5 and 9 or between 6 and 8, and most preferably between 6 and 7, such as 6 to 6.5. In some embodiments, compositions in solid form are packaged in multiple single dose units, each containing a fixed amount of the above-mentioned agent or agents, such as in a sealed package of tablets or capsules. In some embodiments, compositions in solid form are packaged in a container for a flexible quantity, such as in a squeezable tube designed for a topically applicable cream or ointment. Synthesis of Radiopharmaceuticals Comprising Compounds of Formula I [140] Compounds of Formula I comprise conjugates targeting HSP90, which can be radiolabeled with a radionuclide such as Indium-111 ( ¹¹¹ In), Lutetium-177 ( ¹⁷⁷ Lu), or Actinium- 225 ( ²²⁵ Ac) to form radionuclide-chelated radiopharmaceuticals. The synthesis of compounds of Formula I, or their radionuclide-chelated radiopharmaceuticals, can be referred to WO 2020/205948. Below are the synthetic schemes or protocols that can be followed to synthesize the corresponding compounds. A person of ordinary skill in the art would have been able, based on the disclosures provided herein and the knowledge in the field, to prepare the depicted compounds and their structurally similar analogs (e.g., compounds with different chelators such as DOTA, NOTA, and NODA-GA). [141] Synthetic scheme 1. O t O BuO O O O O O O NH ₂ t N N BuO O O ^t Bu N N Coupling agents (PyBOP or HATU or HBTU or CDI) HO O Base (TEA or DIPEA) O _O ^tBu Solvent (THF or DMF) t O BuO O t N N BuO O H O , Pd O ^t Bu ₂ /C O O N N O O O N MeOH H O O ^OtBu NH tBuO O O HO HN N t N N BuO O O O O ^t Bu OH N N O O N N HO O O N H O O _O ^tBu Coupling agents (PyBOP or HATU or HBTU or CDI) Base (TEA or DIPEA) S ^{olvent (THF or DMF)}

^t O BuO O t N N BuO O O O ^t Bu O O N N N O O N H O O ^OtBu 95% TFA, 2.5% TIPS, 2.5% water HO HN N O N N OH O HO O N N HO O O OH O O N N N O O N H O O ^{OH Chemical Formula: C} ₅₆ ^H ₈₄ ^N ₁₀ ^O ₁₇ HO HN Exact Mass: 1168.60 N Molecular Weight: 1169.34 O N N OH [142] Synthetic scheme 2.

^t O BuO O N _H ^{t N N} BuO O O ^t Bu N N HO O O ^OtBu HO HN N Coupling agents (PyBOP or HATU or HBTU or CDI) O Base (TEA or DIPEA) N N OH ^{Solvent (THF or DMF) t} BuO O O HO O N N O tBuO O O ^t N N Bu HO N N O OH N O N N O ^OtBu N O O ^OH 95% TFA, 2.5% TIPS, 2.5% water Chemical Formula: C HO HN ₄₅ H ₆₃ N ₉ O ₁₂ Exact Mass: 921.46 N HO HN N Molecular Weight: 922.05 O OH N N O OH N N [143] Synthetic scheme 3. tBuO O O t N N BuO O O ^t Bu ^t N N O ^O _{O Bu} O HO H O O (S) N N ^H ₂ ^t MeO N N MeO _{(S) O} ^{O Bu} O ^t Bu t O BuO ₂ C ^t BuO N N CO ₂ ^t Bu Coupling agents (PyBOP or HATU or HBTU or CDI) O Base (TEA or DIPEA) ^t BuO O Solvent (THF or DMF) NH O ^O _O ^t _Bu HO HN H O N (S)N HO O LiOH.H ₂ O N N N N O ^t Bu OH t O BuOC ^t BuO THF, MeOH, water ₂ N N Coupling agents (PyBOP or HATU or HBTU or CDI) O t Base (TEA or DIPEA) BuO O Solvent (THF or DMF) O ^O _O ^t _Bu H N O (S) N N N O O ^t Bu t ^BuO _2C ^t BuO N N O 95% TFA, 2.5% TIPS, 2.5% water tBuO O HO HN N O N N OH O ^O _OH H N O (S) N N N O OH CO ₂ H HO N N O HO O HO HN N Chemical Formula: C ₄₉ H ₆₈ N ₁₀ O ₁₅ Exact Mass: 1036.49 O N N Molecular Weight: 1037.14 OH

[144] Synthetic scheme 4. tBuO O t N N BuO O N N _O ^tBu O ^O _O ^tBu O HO H O O (S)N MeO MeO _(S) ^NH _{2 O O} ^tBu N N O _O ^{tBu t} BuO ₂ C ^t BuO 2 ^t N N CO Bu Coupling agents (PyBOP or HATU or HBTU or CDI) O Base (TEA or DIPEA) ^t BuO O Solvent (THF or DMF) O O ^O _O ^t _Bu RO O NH ₂ H O O O (S)N LiOH.H ₂ O HO N N R = Benzyl O O ^t Bu tBuOC ^t THF, MeOH, water ₂ BuO N N Coupling agents (PyBOP or HATU or HBTU or CDI) O t Base (TEA or DIPEA) BuO O Solvent (THF or DMF) NH t O BuO O HO HN N N N tBuO ^t BuO O O ₂ C O ^t N N H N _O ^Bu OH O N N RO O O (S) N H O O _{O O} ^t Coupling agents (PyBOP or HATU or HBTU or CDI) B ^u Base (TEA or DIPEA) R = Benzyl H _{2, Pd-C} ^{Solvent (THF or DMF)} MeOH R = H

^t O BuO O tBuO ^t N N 2C BuO O O H O ^t Bu O N N N N O O _(S) ^N H O O _O ^OtBu 95% TFA, 2.5% TIPS, 2.5% water HO HN N O N N OH O HO O N N HO ₂ C HO O O H OH O N N N N O O _(S) ^N H O O _O ^OH Chemical Formula: C ₅₈ H ₈₅ N ₁₁ O ₁₉ HO HN Exact Mass: 1239.60 N Molecular Weight: 1240.38 O N N OH [145] Synthetic scheme 5. O t O BuO O NH O RO O O ₂ t N N BuO R = Benzyl O O ^t Bu N N HO Coupling agents (PyBOP or HATU or HBTU or CDI) O t Base (TEA or DIPEA) O ^OBu Solvent (THF or DMF) ^t BuO O O O _(S) ^NH ₂ N N MeO tBuO O O ^t Bu N N _CO2 ^tBu RO O O O N H O O Coupling agents (PyBOP or HATU or HBTU or C O ^Ot DI) B ^u R = Benzyl Base (TEA or DIPEA) H _{2, Pd-C} Solvent (THF or DMF) MeOH R = H t O BuO O t N N BuO LiOH.H ₂ O O H O O ^t Bu (S)N O O N N THF, MeOH, water MeO O N H O O ^{t CO2tBu} O OBu NH tBuO O O HO HN N t N N BuO O O O N N H _O ^tBu OH ( N O O N N HO S) O N H O Coupling agents (PyBOP or HATU or HBTU or CDI) O CO ₂ ^t Bu _{O O} ^tBu Base (TEA or DIPEA) Solvent (THF or DMF) t O BuO O t N N BuO O H O _O ^tBu (S)N O O N N N O N H O O CO ₂ ^t Bu O O ^t Bu 95% TFA, 2.5% TIPS, 2.5% water HO HN N O N N OH

O HO O N N HO O H O OH (S) N O O N N N O N H O O CO ₂ H O OH Chemical Formula: C ₅₈ H ₈₅ N ₁₁ O ₁₉ Exact Mass: 1239.60 HO HN Molecular Weight: 1240.38 N O N N OH [146] Synthetic scheme 6. NO O ₂ NH N O Cl O O NO ₂ ^{, Base (TEA or DIPEA)} RO HN RO HN N N (Z) (Z) O N N O OR OR N N R = Benzyl O HO O N N HO O OH 1) H ₂ N O O N N O O N H O O ^OH R = Benzyl 2 ⁾ _{H2, Pd-C} R = H ^O O _OH H O ^O N O N N _{O O} N N H O OH HO N N O HO O HO HN N O OH N N _{Chemical Formula: C56} ^H ₈₅ ^N _11O17 Exact Mass: 1183.61 M ^{olecular Weight: 1184.36} [147] Synthetic scheme 7. O O NH O ₂ N O O NH 1) HO ₂ C ^{O O} N _HBn Coupling agents (PyBOP or HATU or HBTU or CDI) Base (TEA or DIPEA) Solvent (THF or DMF) HO HN N HO HN N ^{, P} O 2 _{) H2} ^d-C N N OH O N N OH O O HO HO O O O Cl N N N N HO O HO O OH O ₂ N O H OH N N N N H ₂ N O N N Ba N O H O se H T ^{EA or DIPEA)} O O OH ⁽ O ₂ N _O ^OH O HO O N N HO O O H H OH O N N N N N ^O _O N O H O O ^OH Chemical Formula: C ₅₈ H ₈₈ N ₁₂ O ₁₇ HO HN Exact Mass: 1224.64 N Molecular Weight: 1225.41 O N N OH Materials and Analytical Assays Provided below are analytical assays for characterizing the compounds of Formula I. [148] Actinium-225 ( ²²⁵ Ac) was supplied by the U.S. Department of Energy Isotope Program in the Office of Science for Nuclear Physics. Lutetium-177 ( ¹⁷⁷ Lu) was received from ITG Isotope Technologies Garching GmbH. Indium-111 ( ¹¹¹ In) was supplied from BWXT. [149] RadioTLC was performed with Bioscan AR-2000 Imaging Scanner, carried out on iTLC- SG glass microfiber chromatography paper (Agilent Technologies, SGI0001) plates or iTLC-SA glass microfiber chromatography paper (Agilent Technologies, A120B12) plates. [150] Radioactive HPLC was performed using a Waters system comprised of a Waters 1525 Binary HPLC pump, a Waters 2489 UV/Visible Detector (monitoring at 254 and 214 nm), and a Bioscan Flow Count radiodetector (FC-3300) and a reverse phase (C18) column. Alternatively, analysis was performed using a Waters Acquity UPLC system comprised of a Waters Acquity Binary Solvent Manager, a Waters Acquity Sample Manager, a Waters Acquity Column Manager (column temperature 30 °C), a Water Acquity Photodiode Array Detector (monitoring 254 nm and 214 nm), a Bioscan Flow Count radiodetector (FC-3300), and a reverse phase (C18) column. [151] Analytical HPLC-MS was performed using a Waters Acquity HPLC-MS system comprised of a Waters Acquity Binary Solvent Manager, a Waters Acquity Sample Manager, a Waters Acquity Column Manager (column temperature 30 °C), a Waters Acquity Photodiode Array Detector (monitoring at 254 nm and 214 nm), a Waters Acquity TQD with electrospray ionization and a Waters Acquity BEH C18, 2.1 x 50 mm (1.7 μm) column. Preparative HPLC was performed using a Waters HPLC system comprised of a Waters 1525 Binary HPLC pump, a Waters 2489 UV/Visible Detector (monitoring at 254 nm and 214 nm) and a Waters XBridge Prep C1819 x 100 mm (5 μm) column. [152] HPLC elution method 1: Waters Acquity BEH C182.1 x 50 mm (1.7 μm) column; mobile phase A: H2O (0.1% v/v TFA); mobile phase B: acetonitrile (0.1% v/v TFA); flow rate = 0.3 mL/min; wavelength = 214, 254 nm; initial = 90% A, 8 min = 0% A, 10 min = 0% A, 11 min = 90% A, 12 min = 90% A. [153] HPLC elution method 2: Waters Acquity BEH C182.1 x 50 mm (1.7 μm) column; mobile phase A: H ₂ O (0.1% v/v TFA); mobile phase B: acetonitrile (0.1% v/v TFA); flow rate = 0.3 mL/min; wavelength = 214, 254 nm; initial = 90% A, 3 min = 0% A, 3.5 min = 0% A, 4 min = 90% A, 5 min = 90% A. [154] HPLC elution method 3: Waters Acquity BEH C182.1 x 50 mm (1.7 μm) column; mobile phase A: H2O (0.1% v/v Formic Acid); mobile phase B: acetonitrile (0.1% v/v Formic Acid); flow rate = 0.3 mL/min; wavelength = 214, 254 nm; initial = 90% A, 3 min = 0% A, 3.5 min = 0% A, 4 min = 90% A, 5 min = 90% A. [155] HPLC elution method 4: Waters Acquity BEH C182.1 x 50 mm (1.7 μm) column; mobile phase A: H2O (0.1% v/v Formic Acid); mobile phase B: acetonitrile (0.1% v/v Formic Acid); flow rate = 0.3 mL/min; wavelength = 214, 254 nm; initial = 90% A, 8 min = 0% A, 10 min = 0% A, 11 min = 90% A, 12 min = 90% A. [156] HPLC elution method 5 (radioHPLC): Phenomenex Gemini 5 μm C18110 Å, LC Column 150 x 4.6 mm; mobile phase A: H2O (0.1% v/v TFA); mobile phase B: acetonitrile (0.1% v/v TFA); flow rate = 1.0 mL/min; wavelength = 214, 254 nm; initial = 100% A, 2 min = 100% A, 10 min = 0% A, 12 min = 0% A, 14 min = 100% A, 15 min = 100% A. [157] HRMS was performed using an Agilent G1969 ESI TOF system. EXAMPLES Example 1: Synthesis of (R)-2,2',2''-(10-(20-Carboxy-1-(4-(4-(3-(2,4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-1,17-dioxo- 4,7,10,13-tetraoxa-16-azaicosan-20-yl)-1,4,7,10-tetraazacycl ododecane-1,4,7-triyl)triacetic acid (Compound A) tBuO ₂ C t ^t BuO BuO ₂ C 2C N N tBuO ₂ C O O N N i) CDI O O N N Bn _CO2 ^tBu O ii) O BnO O O N O O NH N N O O ₂ H CO ^t B C ^t Bu ₂ u HO O _{2 CO2} ^t O B ^u Intermediate 1 - A iii) re-subjected with HBTU, DIPEA Step 1 ^t BuO ₂ C tBuO ₂ C N N O O P ^{d/C; H} (atm), MeOH 2 O O N N ^t HO O O N CO ₂ Bu H CO ₂ ^t Bu Step 2 Intermediate 1 - B NH •HCl t _BuO2C t _BuO2C N N HO HN N O O O O O N N N N CO ₂ ^t Bu OH N O O N H ^t Intermediate 1 - C _{CO2 Bu} HBTU, DIPEA, DMF Step 3 HO HN Intermediate 1 - D N O N N OH H ^O ₂ ^{C HO} ₂ ^C N N O O O O N N N O O N ^CO ₂ ^H H ^{CO H TFA/TIPS/H} _{2 2} ^O Step 4 Compound A HO HN N O N N OH Step 1: Synthesis of 1-Benzyl 21-(tert-butyl) (R)-17-oxo-20-(4,7,10-tris(2-(tert-butoxy)-2- oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,7,10,13-tetr aoxa-16-azahenicosanedioate (Intermediate 1 – A) To a 20 mL scintillation vial was added (R)-DOTAGA(tBu)4 (500 mg, 0.71 mmol, 1 equiv.) and a stir bar followed by anhydrous dichloromethane (3.6 mL) to make a 0.2 M solution. Next CDI (126 mg, 0.74 mmol, 1.1 equiv.) was added and the solution stirred at RT and monitored by HPLC-MS. After 3 h only ~35% conversion was observed, so the reaction was re-dosed with CDI (70 mg, 0.43 mmol, 0.6 equiv.) and stirred at RT for 18.5 h. At this point, an aliquot of the reaction was checked and found to have the same approximate conversion. The reaction solution was transferred into a second vial containing Amino-PEG4-benzyl ester (279 mg, 0.78 mmol, 1.1 equiv.) in anhydrous dichloromethane (1 mL) and stirred at RT. The reaction was monitored by HPLC-MS and after 3h ~29% conversion to product was found with the remainder being DOTAGA(tBu)4 by HPLC-MS. The reaction was worked up by concentration under vacuum and then resubjected to the reaction conditions by adding the following reagents: anhydrous THF (4.6 mL) and HBTU (803 mg, 2.12 mmol, 3 equiv.), at which point the reaction was stirred for 5 minutes before adding DIPEA (0.62 mL) and stirring over the weekend at RT (22.5 °C). After 88 h,the reaction had gone to completion and was worked up by concentration under vacuum. The crude product was purified by reverse phase-C18 column chromatography to afford Intermediate 1 - A (436 mg, 47%, purity: >96%) as a pale-yellow sticky solid, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 4.90 min; MS (positive ESI): found m/z 1038.6 [M+H] ⁺ ; C53H92N5O15 (calc. 1038.6). ¹ H NMR (700 MHz, DMSO-d ₆ ^^į^^^^^^^EU^V^^^+^^^^^^^-7.31 (m, 5H), 5.11 (s, 2H), 4.62-2.65 (multiplets overlapping with H ₂ O, 43H), 2.60 (t, J = 7.0 Hz, 2H), 2.49-2.43 (m, 1H), 2.43-2.35 (m, 1H), 1.47 (br s, 9H), 1.46 (br s, 9H), 1.42 (br s, 9H), 1.40 (br s, 9H); ¹³ C NMR (176 MHz, DMSO-d ₆ ^^į^^^^^^^^^^^^^^^ 158.3 (TFA, q, J = 35.2 Hz), 136.5, 128.4, 128.0, 127.8, 115.8 (TFA, q, J = 299.2 Hz), 83.8 (br), 81.6 (br), 69.8 (2C), 69.7 (2C), 69.6, 69.1, 66.0, 65.4, 54.5 (br), 53.4 (br), 38.5, 34.7, 31.8 (br), 27.8, 27.7, 27.6 (2C). Step 2: Synthesis of (R)-2,2-Dimethyl-4,8-dioxo-5-(4,7,10-tris(2-(tert-butoxy)-2- oxoethyl)- 1,4,7,10-tetraazacyclododecan-1-yl)-3,12,15,18,21-pentaoxa-9 -azatetracosan-24-oic acid (Intermediate 1 - B) To a solution of Intermediate 1 - A (396 mg, 0.30 mmol, 1 equiv.) in anhydrous MeOH (4 mL) in a 20 mL vial was added a stir bar and Pd/C, 10% Pd basis (32 mg, 0.03 mmol, 0.1 equiv.). The reaction mixture was degassed and subjected to H2 atmosphere via a balloon (3X). The reaction was then left to stir at RT (22 deg °C) and monitored by HPLC-MS. After 18 h the reaction was filtered through an Acrodisc One (0.2 μm PTFE) syringe filter into a 20 mL scintillation vial. The reaction vial was then rinsed with MeOH (4 mL), and this was also filtered into the scintillation vial. The crude reaction was then concentrated under vacuum to afford 387 mg of a clear film. The crude product was purified by reverse phase-C18 column chromatography to afford Intermediate 1 - B (237 mg, 66%, purity: 99%) as a clear film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 4.06 min; MS (positive ESI): found m/z 948.7 [M+H] ⁺ ; C46H86N5O15 (calc.948.6). ¹ H NMR (700 MHz, DMSO-d6^^į^ 7.98 (s, 1H), 4.62-2.60 (multiplets overlapping with H2O, 43H), 2.48-2.45 (m, 1H), 2.44 (t, J = 7.0 Hz, 2H), 2.41-2.35 (m, 1H), 1.45 (br s, 18H), 1.41 (br s, 18H); ¹³ C NMR (176 MHz, DMSO- d ₆ ^^į^^^^^^^^^^^^^^^^^^^2 (TFA, q, J = 33.4 Hz), 116.4 (TFA, q, J = 303.8 Hz), 69.8, 69.7 (2C), 69.6 (2C), 69.1, 66.2, 54.6 (br), 53.7 (br), 38.6, 31.8 (br), 27.8, 27.7 (2C), 27.6. Step 3: Synthesis of tri-tert-Butyl 2,2',2''-(10-(24-(4-(4-(3-(2,4-Dihydroxy-5-isopropylphenyl)- 5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2,2-dimethyl-4,8,24-trioxo- 3,12,15,18,21-pentaoxa-9-azatetracosan-5-yl)-1,4,7,10-tetraa zacyclododecane-1,4,7-triyl)(R)- triacetate (Intermediate 1 - D) To a 20 mL vial was added Intermediate 1 - B (14 mg, 15 μmol, 1 equiv.) followed by 1 anhydrous DMF (1 mL) and stir bar. The vessel was then loaded with HBTU (5.6 mg, 15 μmol, 1 equiv.) and lastly DIPEA (12.4 μL, 71 μmol, 5 equiv.) and stirred at RT (22 °C) for 5 min. A solution of Intermediate 1 - C (8 mg, 1 equiv.) in anhydrous DMF (1 mL) was then added, and an additional 1 mL of anhydrous DMF was used to rinse the vial containing the Intermediate and added to the reaction vessel. The resulting solution was stirred at RT (22 °C) and monitored by HPLC-MS. After 1 h the reaction was worked up by concentration under vacuum. The crude product was purified by reverse phase-C18 column chromatography to afford Intermediate 1 - D (12.4 mg, 96%, purity: 96%) as a clear film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 4.72 min; MS (positive ESI): found m/z 1393.9 [M+H] ⁺ ; C ₇₂ H ₁₁₇ N ₁₀ O ₁₇ (calc.1393.8). ¹ H NMR (700 MHz, DMSO-d ₆ + ~10% D ₂ 2^^į^^^^^^^G^^J = 7.0 Hz, 2H), 7.20 (d, J = 7.0 Hz, 2H), 6.55 (s, 1H), 6.33 (s, 1H), 4.35- 0.92 (multiplets overlapping with H2O and DMSO and triplet at 0.99 ppm, 97H), 0.99 (t, J = 7.0 Hz, 3H), 0.76 (d, J = 7.0 Hz, 6H). Step 4: Synthesis of (R)-2,2',2''-(10-(21-Carboxy-1-(4-(4-(3-(2,4-dihydroxy-5-iso propylphenyl)- 5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1- yl)-1,18-dioxo-5,8,11,14-tetraoxa- 2,17-diazahenicosan-21-yl)-1,4,7,10-tetraazacyclododecane-1, 4,7-triyl)triacetic acid (Compound A) To a 20 mL vial was added Intermediate 1 - D (10.4 mg, 6.4 μmol, 1 equiv.) and a stir bar, followed by 2 mL of TFA/TIPS/H2O (95:2.5:2.5 v/v/v). The resulting clear solution was placed in a 3^^°C oil bath and the reaction was monitored by HPLC-MS. After 3 h the reaction was complete and was concentrated under a stream of air. The crude product was purified by reverse phase-C18 column chromatography to afford Compound A (6.5 mg, 75%, purity: >99%) as a white solid, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 3.00 min; HRMS (positive ESI): found m/z 1169.6074 [M+H] ⁺ ; C56H85N10O17 (calc.1169.6089). ¹ H NMR (700 MHz, DMSO-d6 + ~10% D22^^į^^^^^^^G^^J = 7.0 Hz, 2H), 7.20 (d, J = 7.0 Hz, 2H), 6.56 (s, 1H), 6.32 (s, 1H), 4.30 (br d, 2H), 4.05-2.35 (multiplets overlapping with H2O and DMSO, 47H), 1.90-1.80 (br m, 3H), 1.77-1.71 (m, 2H), 1.61-1.55 (m, 3H), 1.11-1.08 (m, 2H), 1.00 (t, J = 7.0 Hz, 3H), 0.98-0.95 (m, 2H), 0.76 (d, J = 7.0 Hz, 6H); ¹³ C NMR (175 MHz, DMSO-d ₆ ^^į^^^^^^^^^^^^5, 157.9 (TFA, app q, J = 31.5 Hz), 157.3, 156.2 (2C), 154.4, 147.8, 141.4, 133.2, 129.6, 127.3, 125.8, 125.5, 117.3 (TFA, app q, J =297.5 Hz), 102.6, 102.5, 69.8 (2C), 69.7 (2C), 69.6, 69.1, 66.9, 53.7, 45.1, 41.7, 41.1, 40.0, 38.6, 37.3, 33.6, 32.9, 32.2, 31.3, 25.3, 22.4, 14.5. Example 2: Synthesis of 2,2',2''-(10-(24-(4-(4-(3-(2,4-Dihydroxy-5-isopropylphenyl)- 5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2,24-dioxo-6,9,12,15,18,21- hexaoxa-3-azatetracosyl)-1,4,7,10-tetraazacyclododecane-1,4, 7-triyl)triacetic acid (Compound B) i) DSC, pyridine, MeCN _CO ^tBu ii) HBTU, DMF ₂ CO ₂ ^t Bu CO ₂ ^t Bu O O ^{N HO} _{N CO} ^tB 2 ^C N N ₂ ^u _O O NH ₂ O 3 ^HO 2 ^C O O N N O O N HO ₂ C N N H 3 ^t BuO ₂ C t Step 1 Intermediate 2 - A BuO ₂ C

NH •HCl CO ₂ ^t Bu BnO HN ^N _N CO ₂ ^t Bu N O O O N N O O N N OBn N O O N H 3 _BuO2 ^t _C Intermediate 2 - B HBTU, DIPEA Step 2 BnO HN Intermediate 2 - C N O N N OBn C _O2 ^t _Bu N _C ^t N _O2 ^Bu O O O O N N ^{Pd/C; H} (atm), MeOH N O O N 2 H 3 BuO ₂ ^t C Step 3 Intermediate 2 - D HO HN N O N N OH C ^O ₂ ^H N N ^CO ₂ ^H O O O O N N N O O N H 3 ^HO _C T ^FA/TIPS/H ₂ ^O ₂ Step 4 Compound B HO HN N O N N OH Step 1: Synthesis of 2-Oxo-1-(4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10- tetraazacyclododecan-1-yl)-6,9,12,15,18,21-hexaoxa-3-azatetr acosan-24-oic acid (Intermediate 2 - A) To a solution of DOTAtris(tert-butyl ester) (50 mg, 0.09 mmol, 1 equiv.) in MeCN (2.0 mL) was added N,N’-disuccinimidyl carbonate (DSC) (32 mg, 0.11 mmol, 1.3 equiv.) and pyridine (0.20 mL, 2.5 mmol, 28 equiv.). The reaction mixture was stirred RT (22.5 °C) and monitored by HPLC-MS. After 70 min ~80% starting material was remaining, so the reaction was dosed with HBTU (34 mg, 0.09 mmol, 1 equiv.) and stirred for 10 min at RT. The reaction mixture was then transferred to a second vial containing Amino-PEG6-acid (64 mg, 0.17 mmol, 2 equiv.) in anhydrous DMF (1 mL, limited solubility) and stirred at RT. The reaction was monitored by HPLC-MS and worked up after 64 hours by concentration under vacuum to afford a clear oil. The crude product was purified by reverse phase-C18 column chromatography to afford Intermediate 2 - A (35 mg, 36%, purity >99%) as a clear film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 3.70 min; MS (positive ESI): found m/z 908.9 [M+H] ⁺ ; C ₄₃ H ₈₂ N ₅ O ₁₅ (calc.908.6). ¹ H NMR (700 MHz, DMSO-d6 + ~10% D22^^į 4.20-2.46 (multiplets overlapping with H2O, triplet at 3.57 ppm J = 7.0 Hz, 2H and DMSO; total 50H), 2.42 (t, J = 7.0 Hz, 2H), 1.44 (br s, 9H), 1.36 (br s, 18H). Step 2: Synthesis of tri-tert-Butyl 2,2',2''-(10-(24-(4-(4-(3-(2,4-bis(benzyloxy)-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-2,24-dioxo- 6,9,12,15,18,21-hexaoxa-3-azatetracosyl)-1,4,7,10-tetraazacy clododecane-1,4,7-triyl)triacetate (Intermediate 2 - C) To a solution of Intermediate 2 - A (30 mg, 26 μmol, 1 equiv.) in MeCN (2 mL) was added HBTU (12 mg, 32 μmol, 1.2 equiv.), and DIPEA (18 μL, 0.11 mmol, 4 equiv.). This was stirred at RT (22.5^°^C) for 10 min before Intermediate 2 - B (22 mg, 32 μmol, 1.2 equiv) was added and the solution was stirred and monitored by HPLC-MS. After 1 h the reaction was worked up by concentrating to dryness under vacuum. The crude product was purified by reverse phase-C18 column chromatography to afford Intermediate 2 - C (35 mg, 77%, purity >99%) as a clear film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 5.52 min; MS (positive ESI): found m/z 1533.7 [M+H] ⁺ ; C ₈₃ H ₁₂₅ N ₁₀ O ₁₇ (calc.1533.9). ¹ H NMR (700 MHz, DMSO-d ₆ + ~10% D22^^į^^^^^-7.26 (m, 8H), 7.19 (d, J = 6.8 Hz, 2H), 7.05 (d, J = 7.6 Hz, 2H), 6.96 (s, 1H), 6.92 (d, J = 8.0 Hz, 2H), 6.67 (s, 1H), 5.01 (s, 2H), 4.88 (s, 2H), 4.27 (d, J = 14.0 Hz, 1H), 3.78 (d, J = 14.0 Hz, 1H), 3.55 (t, J = 7.0 Hz, 2H), 3.49-2.36 (multiplets overlapping with H2O and DMSO, 57H), 1.70-1.63 (m, 1H), 1.52-1.17 (multiplets overlapping with broad 2 singlets at 1.42 ppm and 1.33 ppm, 29H), 1.05-0.98 (m overlapping with triplet at 1.00 ppm J = 7.0 Hz, total 4H), 0.95 (d, J = 7.0 Hz, 6H), 0.92-0.85 (m, 1H). Step 3: Synthesis of tri-tert-Butyl 2,2',2''-(10-(24-(4-(4-(3-(2,4-dihydroxy-5-isopropylphenyl)- 5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2,24-dioxo-6,9,12,15,18,21- hexaoxa-3-azatetracosyl)-1,4,7,10-tetraazacyclododecane-1,4, 7-triyl)triacetate (Intermediate 2 - D) To a solution of Intermediate 2 - C (28.3 mg, 16.1 μmol, 1 equiv.) in MeOH (2.5 mL) in a microwave vial was added a stir bar and Pd/C, 10% Pd basis (7 mg, 6 μmol 0.4 equiv.). The reaction mixture was degassed and subjected to H ₂ atmosphere via a balloon (3X). The reaction was then left to stir at RT (23 °C) and monitored by HPLC-MS. After 16 h the reaction was filtered through an Acrodisc PSF syringe filter into a 20 mL scintillation vial. The reaction vial was rinsed with MeOH (2 x1.5 mL), and this was also filtered into the scintillation vial. The crude reaction was then concentrated crude under vacuum to afford a 23 mg of a yellow film. The crude product was dissolved in MeOH (2 mL) and stirred with SiliaMetS ^® Thiol (SH) Metal scavenger resin (200 mg, 40-63 μm, loading =1.46 mmol/g) to remove apparent Pd coordination in a 37 °C oil bath and was monitored by HPLC-MS. After 1 h the reaction was filtered through an Acrodisc PSF syringe filter into a 20 mL scintillation vial. The reaction vial was rinsed with MeOH (2 x 1.5 mL), and this was also filtered into the scintillation vial. The crude reaction was then concentrated crude under vacuum to afford Intermediate 2 - D (20.8 mg, 81%, purity >97%) as a clear film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 4.45 min; MS (positive ESI): found m/z 1354.3 [M+H] ⁺ ; C ₆₉ H ₁₁₃ N ₁₀ O ₁₇ (calc.1353.8). ¹ H NMR (700 MHz, DMSO-d ₆ + ~10% D ₂ 2^^į^^^^^^^G^^J = 7.0 Hz, 2H), 7.20 (d, J = 7.0 Hz, 2H), 6.55 (s, 1H), 6.32 (s, 1H), 4.30 (br d, J = 14.0 Hz, 1H), 4.20- 2.36 (multiplets overlapping with H2O, triplet at 3.57 ppm J = 7.0 Hz, q at 3.14 ppm, J = 7.0 Hz and DMSO, 60H), 1.76-1.70 (m, 1H), 1.62-1.55 (m, 2H), 1.49 (br s, 9H), 1.34 (br s, 18H), 1.12- 1.06 (m, 1H), 1.01-0.92 (m overlapping with triplet at 0.99 ppm J = 7.0 Hz, total 4H), 0.77 (d, J = 7.0 Hz, 6H). Step 4: Synthesis of 2,2',2''-(10-(24-(4-(4-(3-(2,4-Dihydroxy-5-isopropylphenyl)- 5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2,24-dioxo-6,9,12,15,18,21- hexaoxa-3-azatetracosyl)-1,4,7,10-tetraazacyclododecane-1,4, 7-triyl)triacetic acid (Compound B) To a 20 mL vial was added Intermediate 2 - D (18.0 mg, 11.4 μmol, 1 equiv.), and a stir bar followed by 2 mL of TFA/TIPS/H2O (95:2.5:2.5 v/v/v). The resulting clear solution was placed in a 37 °C oil bath and the reaction was monitored by HPLC-MS. After 2.5 h the reaction was complete and was subsequently concentrated under vacuum. The crude product was purified by reverse phase-C18 column chromatography to afford Compound B (4.6 mg, 29%, purity: 99%) as a white solid, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 3.15 min; HRMS (positive ESI): found m/z 1185.6386 [M+H] ⁺ ; C57H89N10O17 (calc.1185.6402). ¹ H NMR (700 MHz, DMSO-d6 + ~10% D22^^į^^^^^^^G^^J = 7.0 Hz, 2H), 7.20 (d, J = 7.0 Hz, 2H), 6.56 (s, 1H), 6.32 (s, 1H), 4.30 (br d, J = 14.0 Hz, 2H), 4.10-2.38 (multiplets overlapping with H2O and DMSO, 57H), 1.76-1.68 (m, 2H), 1.63-1.52 (m, 3H), 1.13-1.07 (m, 1H), 0.99-0.93 (m overlapping with triplet at 0.99 ppm J = 7.0 Hz, total 4H), 0.77 (d, J = 7.0 Hz, 6H). Example 3: Synthesis of 2,2',2''-(10-(42-(4-(4-(3-(2,4-Dihydroxy-5-isopropylphenyl)- 5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2,42-dioxo- 6,9,12,15,18,21,24,27,30,33,36,39-dodecaoxa-3-azadotetracont yl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetic acid (Compound C) CO ₂ ^t Bu i) DSC, pyridine, MeCN CO ₂ ^t Bu ii) HBTU, DMF C _O ^t _CO ^t N N ₂ ^Bu N N ₂ ^{Bu HO} ₂ ^C O O O O NH ₂ O HO ₂ C N N 9 ^HO2C O O N N O O N H tBuO ₂ C 9 Step 1 Intermediate 3 - A ^t BuO ₂ C

NH •HCl BnO HN ^t N CO ₂ Bu O ^{t N} _N CO ₂ Bu OBn N N O O O O N N Intermediate 2 - B N O O N HBTU, DIPEA H 9 ^t BuO ₂ C Step 2 Intermediate 3 - B BnO HN N O OBn N N CO ₂ ^t Bu t N N CO ₂ Bu O O O O N N (atm), MeOH N O O N Pd/C; H ₂ H 9 ^t BuO ₂ C Step 3 Intermediate 3 - C HO HN N O OH N N C _O2 ^H N N CO ₂ H O O O O N N N O O N H 9 HO ₂ C TFA/TIPS/H ₂ O Step 4 Compound C HO HN N O OH N N Step 1: Synthesis of 2-oxo-1-(4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10- tetraazacyclododecan-1-yl)-6,9,12,15,18,21,24,27,30,33,36,39 -dodecaoxa-3-azadotetracontan- 42-oic acid (Intermediate 3 – A) To a solution of DOTAtris(tert-butyl ester) (50 mg, 0.09 mmol, 1 equiv.) in MeCN (2.0 mL) was added N,N’-disuccinimidyl carbonate (DSC) (32 mg, 0.11 mmol, 1.3 equiv.) and pyridine (0.20 mL, 2.5 mmol, 28 equiv.). The reaction mixture was stirred at RT (22.5 °C) and monitored by HPLC-MS. After 70 min, ~80% starting material remained, so the reaction was dosed with HBTU (34 mg, 0.09 mmol, 1 equiv.) and stirred for 10 min at RT. The reaction mixture was then transferred to a second vial containing Amino-PEG12-acid (81 mg, 0.13 mmol, 1.5 equiv.) in anhydrous DMF (1 mL, limited solubility) and stirred at RT. The reaction was monitored by HPLC-MS and worked up after 64 hours by concentration under vacuum to afford a clear oil. The crude product was purified by reverse phase-C18 column chromatography to afford Intermediate 3 – A (49 mg, 32%, purity 80%) as a clear film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 3.70 min; MS (positive ESI): found m/z 1173.2 [M+H] ⁺ ; C55H106N5O21 (calc. 1172.7). Step 2: Synthesis of tri-tert-Butyl 2,2',2''-(10-(42-(4-(4-(3-(2,4-bis(benzyloxy)-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-2,42-dioxo- 6,9,12,15,18,21,24,27,30,33,36,39-dodecaoxa-3-azadotetracont yl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetate (Intermediate 3 - B) To a solution of Intermediate 3 - A (49 mg, 35 μmol, 1 equiv.) in MeCN (2 mL) was added HBTU (14 mg, 46 μmol, 1.3 equiv.), DIPEA (24 μL, 0.14 mmol, 5 equiv.), and a stir bar. The reaction was stirred at RT (22.5 °C) for 10 min and before Intermediate 2 – B (26 mg, 38 μmol, 1.3 equiv.) was added and the solution was stirred and monitored by HPLC-MS. After 1 h the reaction was worked up by concentrating to dryness under vacuum. The crude product was purified by reverse phase-C18 column chromatography to afford Intermediate 3 - B (40 mg, 70%, purity >99%) as a clear film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 5.40 min; MS (positive ESI): found m/z 1797.9 [M+H] ⁺ ; C95H149N10O23 (calc.1798.1). ¹ H NMR (700 MHz, DMSO-d6 + ~10% D2O) į^^^^^-7.26 (m, 8H), 7.19 (d, J = 7.0 Hz, 2H), 7.05 (d, J = 7.0 Hz, 2H), 6.96 (s, 1H), 6.92 (d, J = 7.0 Hz, 2H) 6.67 (s, 1H), 5.01 (s, 2H), 4.88 (s, 2H), 4.27 (br d, J = 14.0 Hz, 1H), 3.78 (br d, J = 14.4 Hz, 1H), 3.55 (t, J = 7.0 Hz, 2H), 3.52-2.37 (multiplets overlapping with H2O and DMSO, 81H), 1.69-1.63 (m, 1H), 1.52-1.38 (m overlapping with br s at 1.42 ppm, 12H), 1.34 (br s, 18H), 1.05-0.98 (m overlapping with triplet at 1.00 ppm J = 7.0 Hz, total 4H), 0.96 (d, J = 7.0 Hz, 6H). Step 3: Synthesis of tri-tert-Butyl 2,2',2''-(10-(42-(4-(4-(3-(2,4-dihydroxy-5-isopropylphenyl)- 5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2,42-dioxo- 6,9,12,15,18,21,24,27,30,33,36,39-dodecaoxa-3-azadotetracont yl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetate (Intermediate 3 - C) To a solution of Intermediate 3 - B (33 mg, 0.02 mmol, 1 equiv.) in MeOH (2.5 mL) in a microwave vial was added a stir bar and Pd/C, 10% Pd basis (7 mg, 6 μmol 0.4 equiv.). The reaction mixture was degassed and subjected to H2 atmosphere via a balloon (3X). The reaction was then left to stir at RT (23 °C) and monitored by HPLC-MS. After 16 h the reaction was filtered through an Acrodisc PSF syringe filter into a 20 mL scintillation vial.The reaction vial was rinsed with MeOH (2 x1.5 mL), and this was also filtered into the scintillation vial. The crude reaction was then concentrated under vacuum to afford 30 mg of a pale-yellow film. The crude mixture was then dissolved in MeOH (3 mL) and half was stirred with with SiliaMetS ^® Thiol (SH) Metal scavenger resin (200 mg, 40-63 μm, loading =1.46 mmol/g) to remove apparent Pd coordination in a 50 °C oil bath, with monitoring by HPLC-MS. After 2 h the reaction was filtered through an Acrodisc PSF syringe filter into a 20 mL scintillation vial. The reaction vial was rinsed with MeOH (2 x 2 mL), and this was also filtered into the scintillation vial. The crude reaction was then concentrated crude under vacuum. This protocol was repeated with the 2 ^nd half of the crude material and combined to afford Intermediate 3 – C (19.8 mg, 66%, purity >99%) as a clear film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 4.40 min; MS (positive ESI): found m/z 1618.2 [M+H] ⁺ ; C ₈₁ H ₁₃₇ N ₁₀ O ₂₃ (calc.1618.0). ¹ H NMR (700 MHz, DMSO-d ₆ + ~10% D ₂ 2^^į^^^^^^^EU^ d, J = 7.0 Hz, 2H), 7.19 (br d, J = 7.0 Hz, 2H), 6.56 (s, 1H), 6.32 (s, 1H), 4.41-2.37 (multiplets overlapping with H2O, d at 3.83 ppm J = 14.7 Hz, t at 3.57 ppm, J = 7.0Hz, q at 3.14 ppm, J = 7.0 Hz and DMSO, 85H), 1.75-1.68 (m, 1H), 1.62-1.52 (m, 2H), 1.51-1.04 (multiplet overlapping with br singlets at 1.42, 1.34 and 1.18 ppm, 28H), 1.00-0.92 (triplet at 0.99 ppm overlapping with multiplet, 4H), 0.76 (br d, J = 7.0 Hz, 6H). Step 4: Synthesis of 2,2',2''-(10-(42-(4-(4-(3-(2,4-Dihydroxy-5-isopropylphenyl)- 5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2,42-dioxo- 6,9,12,15,18,21,24,27,30,33,36,39-dodecaoxa-3-azadotetracont yl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetic acid (Compound C) To a 20 mL vial was added Intermediate 3 - C (18.0 mg, 9.8 μmol, 1 equiv.) and a stir bar, followed by 2 mL of TFA/TIPS/H ₂ O (95:2.5:2.5 v/v/v). The resulting clear solution was placed in a 37 °C oil bath and the reaction was monitored by HPLC-MS. After 2.5 h the reaction appeared complete and was worked up by transferring to a 50 mL Falcon tube. The reaction vial was washed with TFA (2x0.5 mL), and this was also added to the Falcon tube. The Falcon tube was cooled in an ice bath and thenEt2O (pre-chilled in the ice bath) was added up to the 45 mL mark. After 5 min in the ice bath the flask was centrifuged (5 min, 4^^ C, 3700 rpm) to afford an off-white pellet. The Et2O layer was decanted into a round bottomed flask, and the pellet was dissolved in ACN/H2O (2 mL, 1:1 v/v) and transferred to a tared 20 mL scintillation vial. The Falcon tube was rinsed with additional ACN/H ₂ O (2x2 mL, 1:1 v/v), which was added to the scintillation vial and concentrated under vacuum to afford 9 mg of crude product as a clear film. The crude product was purified by reverse phase-C18 column chromatography to afford Compound C (6.6 mg, 40%, purity: 97%) as a white solid, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 3.27 min; HRMS (positive ESI): found m/z 1487.7508 [M+K] ⁺ ; C69H112KN10O23 (calc.1487.7533). ¹ H NMR (700 MHz, DMSO- d6 + ~10% D22^^į^^^^^^^G^^J = 7.0 Hz, 2H), 7.20 (d, J = 7.0 Hz, 2H), 6.55 (s, 1H), 6.32 (s, 1H), 4.30 (br d, J = 14.0 Hz, 1H), 4.10-2.37 (multiplets overlapping with H2O and DMSO, 84H), 1.76-1.71 (m, 1H), 1.61-1.54 (m, 2H), 1.13-1.06 (m, 1H), 1.01-0.92 (m overlapping with triplet at 0.99 ppm J = 7.0 Hz, total 4H), 0.77 (d, J = 7.0 Hz, 6H). Example 4: Synthesis of (R)-2,2',2''-(10-(21-Carboxy-1-(4-(4-(3-(2,4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-1,18-dioxo- 5,8,11,14-tetraoxa-2,17-diazahenicosan-21-yl)-1,4,7,10-tetra azacyclododecane-1,4,7- triyl)triacetic acid (Compound D) CO ₂ ^t Bu CO H ₂ ^t Bu HO CO ₂ ^t Bu H ₂ N O O O O N CO ₂ ^t Bu N ^N O O NH ₂ H ₂ N O O _N ^N O O HBTU, DIPEA N ^t _N ^N BuO ^t _{N 2} C BuO ₂ C tBuO ₂ C ^t S _t ^{Intermediate 4 - A BuO} _{2C ep 1} O CO ^t Bu H ₂ O O N CO ^t Bu ) 4-Nitrophenylchloroformate, DIPEA N N ₂ i O O H _N ^N O ⁱⁱ⁾ NH •HCl Intermediate 4 - B ^t _N ^N BuO ₂ C tBuO ₂ C HO HN N H O HO N OH N N N O OH N N Intermediate 1 - C Step 2 O CO H H ₂ O O N CO ₂ H N N O O H _N ^N TFA/TIPS/H ₂ O O S _{tep 3} Compound D HO ^{N N} 2C HO ₂ C HO HN N O OH N N Step 1: Synthesis of tri-tert-Butyl 2,2',2''-(10-(1-amino-22,22-dimethyl-16,20-dioxo-3,6,9,12,21 - pentaoxa-15-azatricosan-19-yl)-1,4,7,10-tetraazacyclododecan e-1,4,7-triyl)(R)-triacetate (Intermediate 4 - A) A 20 mL scintillation vial was charged with (R)-DOTAGA( ^t Bu)4 (1.00g, 1.41 mmol, 1 equiv), amino-PEG4-amine (511 mg, 2.12 mmol, 1.5 equiv), HBTU (607 mg, 1.56 mmol, 1.1 equiv), anhydrous acetonitrile and lastly DIPEA (1.24 mL, 7.06 mmol, 5 equiv). The reaction was stirred at RT (22^^C) and monitored by HPLC-MS. After 2 h the reaction was worked up by concentration under vacuum to afford a pale yellow oil. The crude product was purified by reverse phase-C18 column chromatography to afford Intermediate 4 - A (448 mg, 26%, purity: >93%) as a clear sticky film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 3.63 min; MS (positive ESI): found m/z 919.5 [M+H] ⁺ ; C45H87N6O13 (calc.919.6). ¹ H NMR (700 MHz, DMSO-d ₆ + ~10% D ₂ 2^^į^^^^^-2.30 (multiplets including overlap with H ₂ O and DMSO, 45H), 1.92-1.80 (br m, 1H), 1.69-1.57 (br m, 1H), 1.44 (br s, 18H), 1.33 (br s, 9H), 1.31 (br s, 9H). Step 2: Synthesis of tri-tert-Butyl 2,2',2''-(10-(1-(4-(4-(3-(2,4-dihydroxy-5-isopropylphenyl)-5 - (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-24,24-dimethyl-1,18,22-trioxo- 5,8,11,14,23-pentaoxa-2,17-diazapentacosan-21-yl)-1,4,7,10-t etraazacyclododecane-1,4,7- triyl)(R)-triacetate (Intermediate 4 - B) To a solution of Intermediate 4 – A (50 mg, 41 μmol, 1 equiv) in anhydrous THF (1 mL) and stir bar was added DIPEA (28.7 μL, 164 μmol, 4 equiv) and cooled to 0 °C, followed by addition of 4-nitrophenylchloroformate (8.6 mg, 41 μmol, 1 equiv) at 0 °C in one portion. Following the addition the reaction was removed from the icebath to stir at RT (21.5^^C), purged with an argon balloon and monitored by HPLC-MS. After 45 min observed complete conversion to the nitrophenyl intermediate and proceeded to add Intermediate 1 - C (24 mg, 46 μmol, 1.1 equiv) directly to the reaction followed by DIPEA (7.2 μL, 46 μmol, 1.1 equiv) and lastly purged the reaction with an argon balloon. The reaction was stirred at RT and monitored by HPLC-MS. After 1 h anhydrous DMF (1 mL) was added which resulted in a homogeneous solution and the reaction was continued to stir at RT and monitored by HPLC-MS. After 1 h the reaction temperature was elevated to 50^^C and monitored by HPLC- MS. After 43 h the reaction was redosed with DIPEA (28.7 μL, 164 μmol, 4 equiv), purged with an argon balloon and stirred in the 50^^C bath for an additional 21 h which resulted in complete conversion. The reaction was then worked up by concentration under vacuum to afford a yellow film. The crude product was purified by reverse phase-C18 column chromatography to afford Intermediate 4 - B (26 mg, 38%, purity: >98%) as a clear film, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.42 min; MS (positive ESI): found m/z 1408.8 [M+H] ⁺ ; C72H118N11O17 (calc.1408.9). ¹ H NMR (700 MHz, DMSO-d6 + ~10% D22^^į^^^^^^^G^^J = 8.0 Hz, 2H), 7.21 (d, J = 7.9 Hz, 2H), 6.56 (s, 1H), 6.35 (s, 1H), 4.38- 2.29 (multiplets including overlap with H2O and DMSO, 55H), 1.67-1.59 (m, 2H), 1.52 (br d, J = 12.9 Hz, 2H), 1.50-1.21 (4 broad singlets overlapping, 36H), 1.04-0.94 (m overlapping with t at 0.99 ppm with J = 7.2 Hz, 5H total), 0.75 (d, J = 7.0 Hz, 6H). Step 3: Synthesis of (R)-2,2',2''-(10-(21-Carboxy-1-(4-(4-(3-(2,4-dihydroxy-5-iso propylphenyl)- 5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1- yl)-1,18-dioxo-5,8,11,14-tetraoxa- 2,17-diazahenicosan-21-yl)-1,4,7,10-tetraazacyclododecane-1, 4,7-triyl)triacetic acid (Compound D) To a 20 mL vial was added Intermediate 4 - B (16.2 mg, 9.7 μmol, 1 equiv), stir bar followed by 2 mL of TFA/TIPS/H ₂ O (95:2.5:2.5 v/v/v). The resulting clear solution was placed in a 37 ^^C oil bath and the reaction was monitored by HPLC-MS. After 3.5 h the reaction had went to completion and was concentrated under a stream of air. The crude product was purified by reverse phase-C18 column chromatography to afford Compound D (10 mg, 72%, purity: >99%) as a white solid, TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 2.97 min; HRMS (positive ESI): found m/z 1184.6175 [M+H] ⁺ ; C56H86N11O17 (calc.1184.6198). ¹ H NMR (700 MHz, DMSO-d6 + ~10% D ₂ 2^^į^^^^^^^G^^J = 7.0 Hz, 2H), 7.20 (d, J = 7.0 Hz, 2H), 6.55 (s, 1H), 6.33 (s, 1H), 4.10-2.30 (multiplets including overlap with H ₂ O and DMSO, 52H), 1.95-1.77 (m, 3H), 1.68- 1.59 (m, 2H), 1.52 (app br d, J = 14.0 Hz, 2H), 1.03-0.97 (m overlapping with triplet at 0.99 ppm with J = 7.1 Hz, 5H total), 0.76 (d, J = 7.1 Hz, 6H). Example 5: Synthesis of (R)-2,2',2''-(10-(22-Carboxy-1-(4-(4-(3-(2,4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-1,14,19- trioxo-4,7,10-trioxa-13,15,18-triazadocosan-22-yl)-1,4,7,10- tetraazacyclododecane-1,4,7- triyl)triacetic acid (Compound E) t _B ^O O _uO t _B ^O O _uO tBuO ^N _{N FmocHN} ^{t N} _N ^{1. HBTU, DIPEA, DMF} O N ^H ₂ + BuO O _{H N N N} ^Ot Bu N _N ^Ot Bu ₂ 2. Piperidine N H HO ^t O O S _O ^{O Bu Ot} tep 1 O ^Bu Intermediate 5-A t ^O O _BuO 1. p-NO ₂ -Phenyl chloroformate ^t BuO ^N _N DIPEA, THF O H H O ^t O N N _{N N} ^O Bu O O O N O H O ^t O 2. O _O ^{O Bu} O O _O ^NH ₂ Step 2 Intermediate 5-B _Bu ^{t O} O _O t ^N _N LiOH BuO O H H O ^t N _{N N} ^O Bu THF:H ₂ O O N HO O O N H O O ^t O OBu Step 3 Intermediate 5-C NH.HCl B ^{t O} O _uO BuO ^{t N} _N O H H O ^t O N N _{N N} ^O Bu HO O N O O N N H O O N _O ^OtBu N N H OH Intermediate 1-C HO O HBTU, DIPEA, DMF N N Step 4 H OH N N Intermediate 5-D H _O ^O O HO ^N _N O H H O O N N _{N N} ^OH N O O N H O O TFA:TIPS:H ₂ O 95:2.5:2.5 O OH 37 °C Step 5 HO O N N H OH N N ^{Compound E} Step 1: Synthesis of tri-tert-Butyl 2,2',2''-(10-(5-((2-aminoethyl)amino)-1-(tert-butoxy)-1,5- dioxopentan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl )(R)-triacetate (Intermediate 5- A): To a 20 mL scintillation vial with a stir bar was added, (R)-5-(tert-butoxy)-5-oxo-4-(4,7,10- tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododec an-1-yl)pentanoic acid - (R)- DOTAGA( ^t Bu) ₄ (1.50 g, 2.09 mmol, 1 equiv.), mono-Fmoc ethylene diamine hydrochloride (817 mg, 2.51 mmol, 1.2 equiv.), HBTU (900 mg, 2.09 mmol, 1.1 equiv.) and then charged with anhydrous acetonitrile (11 mL) and then DIPEA (1.84 mL, 1370 mg, 10.46 mmol, 5 equiv.) and stirred at RT. Reaction monitored by HPLC-MS and stopped after 18 h and solvent evaporated under vacuum to give the crude product, which was subjected to Fmoc deprotection. To the crude product dissolved in anhydrous DMF (8 mL) was added piperidine (2 mL) and the resulting clear orange solution was stirred at RT. Reaction stopped after 30 min and solvent evaporated. The obtained crude product was purified by RP chromatography to give Intermediate 5-A (550 mg, 24%, purity: 90%) as white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 3.55 min; MS (positive ESI): found m/z 743.5 [M+H] ⁺ ; C37H71N6O9 (calc.743.5). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C37H71N6O9743.5277; Found 743.5291. ¹ H NMR (700 MHz, DMSO-d6 + 10% D2O) 4.40 – 4.17 (m, 2H), 3.82 – 3.43 (m, 8H), 3.40 – 2.88 (m, 9H), 2.87 – 2.79 (m, 2H), 2.62 (br s, 2H), 2.60 (br s, 3H), 2.47 – 2.38 (m, 2H), 1.98 – 1.79 (m, 1H), 1.65 (s, 1H), 1.54 – 1.26 (m, 36H). *Protons obscured by H ₂ O and DMSO not reported. Step 2: Synthesis of 23-(tert-Butyl) 1-methyl (R)-14,19-dioxo-22-(4,7,10-tris(2-(tert-butoxy)-2- oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,7,10-trioxa- 13,15,18-triazatricosanedioate (Intermediate 5-B) To a solution of tri-tert-butyl 2,2',2''-(10-(5-((2-aminoethyl)amino)-1-(tert-butoxy)-1,5- dioxopentan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl )(R)-triacetate (Intermediate 5-A) (50 mg, 0.07 mmol, 1 equiv.) in anhydrous THF (3 mL) and stir bar was added DIPEA (35.5 μL, 0.20 mmol, 3 equiv.) and cooled to 0 °C, followed by addition of 4-nitrophenylchloroformate (14.1 mg, 0.07 mmol, 1 equiv.) at 0 °C in one portion. Following the addition, the reaction was brought to RT and monitored by HPLC-MS. After 30 min complete conversion to the nitrophenyl intermediate was observed by HPLC-MS. Added methyl 3-(2-(2-(2- aminoethoxy)ethoxy)ethoxy)propanoate (30.4 mg, 0.13 mmol, 2 equiv.) dissolved in anhydrous DMF (1 mL) to the reaction followed by DIPEA (23.6 μL, 0.13 mmol, 2 equiv.) under argon. Continued stirring at room temperature, after 16 hours, the reaction was stopped and concentrated under vacuum, followed by RP chromatography to afford Intermediate 5-B (25 mg, 36 %, purity: 98%) as white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.24 min; MS (positive ESI): found m/z 1004.6 [M+H] ⁺ ; C48H90N7O15 (calc. 1004.6). ¹ H NMR (700 MHz, DMSO-d6) į 7.94 (s, 1H), 6.07 (s, 1H), 5.98 (s, 1H), 4.32-3.68 (br s, 15H), 3.62 (t, J = 6.2 Hz, 2H), 3.59 (s, 3H), 3.52 – 3.47 (m, 2H), 3.49 (s, 6H), 3.36 (t, J = 5.8 Hz, 2H), 3.13 (t, J = 5.8 Hz, 2H), 3.09 – 2.92 (m, 6H), 2.54 (t, J = 6.2 Hz, 2H), 2.07 (s, 4H), 1.61 – 1.27 (m, 42H). Step 3: Synthesis of (R)-2,2-Dimethyl-4,8,13-trioxo-5-(4,7,10-tris(2-(tert-butoxy )-2-oxoethyl)- 1,4,7,10-tetraazacyclododecan-1-yl)-3,17,20,23-tetraoxa-9,12 ,14-triazahexacosan-26-oic acid (Intermediate 5-C) To a flask containing Intermediate 5-B (32 mg, 0.03 mmol, 1 equiv.) was added THF (2 mL) and water (1 mL) and placed in an ice bath and stirred for 10 min. Lithium hydroxide, anhydrous, (2.96 mg, 0.12 mmol) was added as solid in one portion, and the reaction was continued in the ice-water bath. The reaction was monitored by HPLC-MS, and after 1h brought to RT and continued to stir overnight. The reaction solution was acidified (pH ~4) with Amberlite IR120 [H], ~200 mg by stirring for 10 min at RT, then filtered to remove resin. The resin was further washed with ACN, MeOH and then the solvent was evaporated under vacuum. The crude product was dissolved in 1:1 ACN/water/0.1TFA mixture and subjected to lyophilization, to give crude Intermediate 5-C (29 mg, 87%, purity 90%). An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.15 min; MS (positive ESI): found m/z 991.3 [M+H] ⁺ ; C47H88N7O15 (calc.990.6). Step 4: Synthesis of tri-tert-Butyl 2,2',2''-(10-(26-(4-(4-(3-(2,4-dihydroxy-5-isopropylphenyl)- 5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2,2-dimethyl-4,8,13,26-tetraoxo- 3,17,20,23-tetraoxa-9,12,14-triazahexacosan-5-yl)-1,4,7,10-t etraazacyclododecane-1,4,7- triyl)(R)-triacetate (Intermediate 5-D) To a 20 mL scintillation vial with a stir bar was added Intermediate 5-C, (19.9 mg, 0.02 mmol, 1 equiv.) and DMF (2 mL). The reaction mixture was cooled to 0 °C and DIPEA (13.8 μL, 10.2 mg, 0.08 mmol, 4 equiv.), followed by HBTU (7.7 mg, 0.04 mmol, 1 equiv.) was added and stirred for 10 min at 0 °C. The solution was brought to RT and stirred for 30 min and then Intermediate 1-C (10 mg, 0.02 mmol, 1 equiv.) was added as solid. Stirred at RT and reaction monitored by HPLC-MS. The reaction was stopped after 2 h and solvent evaporated under vacuum to give the crude product, which was purified by preparative HPLC to afford Intermediate 5-D (21.4 mg, 64%, purity: 99%) as white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 2.39 min; MS (positive ESI): found m/z 1435.4 [M+H] ⁺ ; C ₇₃ H ₁₁₉ N ₁₂ O ₁₇ (calc.1435.9). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C ₇₃ H ₁₁₉ N ₁₂ O ₁₇ 1435.8811; Found 1435.8833. ¹ H NMR (700 MHz, DMSO-d6) į 9.82 (br s, 1H), 8.95 (t, J = 5.9 Hz, 1H), 7.97 (br s, 1H), 7.29 – 7.24 (m, 4H), 7.10 (br s, 2H), 6.57 (s, 1H), 6.36 (s, 1H), 6.06 (br s, 1H), 5.97 (br s, 1H), 4.36 (d, J = 13.1 Hz, 1H), 3.98 – 3.74 (m, 12H), 3.61 (t, J = 6.7 Hz, 2H), 3.53 – 3.47 (m, 9H), 3.37 (t, J = 5.7 Hz, 2H), 3.19 – 3.12 (m, 5H), 3.07 (s, 3H), 3.01 (s, 3H), 2.94 – 2.87 (m, 2H), 2.60 – 2.51 (m, 4H), 2.49 – 2.42 (m, 2H), 2.07 (s, 4H), 1.81 – 1.73 (m, 1H), 1.66 – 1.57 (m, 2H), 1.52 – 1.31 (m, 42H), 1.17 – 1.10 (m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 1.01 – 0.98 (m, 1H), 0.81 (d, J = 6.9 Hz, 6H). Step 5: (R)-2,2',2''-(10-(22-Carboxy-1-(4-(4-(3-(2,4-dihydroxy-5-iso propylphenyl)-5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-1,14,19-trioxo-4,7,10-trioxa- 13,15,18-triazadocosan-22-yl)-1,4,7,10-tetraazacyclododecane -1,4,7-triyl)triacetic acid (Compound E) To a 20 mL scintillation vial with a stir bar was added Intermediate 5-D (37 mg, 0.03 mmol) and 4.5 mL of deprotection cocktail TFA:TIPS:H2O - 95:2.5:2.5 at RT. The reaction was brought to 37 °C by placing on a pre-heated oil bath at 37 °C and monitored by HPLC-MS. The reaction was stopped after 3h and reaction mixture placed under stream of air to remove TFA. The crude product was purified by preparative HPLC to afford Compound E (20 mg, 54%, purity: 99%) as a white solid TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 3.02 min; MS (positive ESI): found m/z 1211.5 [M+H] ⁺ ; C57H87N12O17 (calc.1211.6). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C57H87N12O17 1211.6307; Found 1211.6330. ¹ H NMR (700 MHz, DMSO-d6) į 12.98 (s, 3H), 10.65 (s, 1H), 9.83 (s, 1H), 8.94 (t, J = 5.9 Hz, 1H), 7.87 (s, 1H), 7.26 (s, 4H), 6.57 (s, 1H), 6.37 – 6.34 (m, 1H), 6.18 (s, 1H), 6.05 (s, 1H), 4.36 (d, J = 12.8 Hz, 1H), 4.05 – 3.73 (m, 11H), 3.61 (t, J = 6.8 Hz, 2H), 3.53 – 3.47 (m, 10H), 3.37 (t, J = 5.8 Hz, 2H), 3.22 – 3.10 (m, 5H), 3.07 – 2.99 (m, 4H), 2.96 – 2.87 (m, 3H), 2.60 – 2.51 (m, 4H), 2.46 (td, J = 12.9, 2.9 Hz, 1H), 2.35 (s, 3H), 1.88 (s, 2H), 1.80 – 1.73 (m, 1H), 1.63 (d, J = 12.7 Hz, 1H), 1.59 (d, J = 13.0 Hz, 1H), 1.18 – 1.10 (m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 1.02 – 0.96 (m, 1H), 0.81 (d, J = 6.9 Hz, 6H). *Protons obscured by H2O and DMSO not reported. Example 6: Synthesis of 2,2',2''-(10-((15S,20R)-20-Carboxy-15-(carboxymethyl)-1-(4-( 4-(3- (2,4-dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2, 4-triazol-4-yl)benzyl)piperidin-1- yl)-1,14,17-trioxo-4,7,10-trioxa-13,16-diazaicosan-20-yl)-1, 4,7,10-tetraazacyclododecane-1,4,7- triyl)triacetic acid (Compound F) ^t _BuO ^{O t} _BuO ^O O O O ^t Bu HBTU, DIPEA, DMF O ^t Bu LiOH tBuO ^N _N ^t BuO ^N _N O O ^t O O THF:H Bu ^t B ₂ O N ^O _{N N} ^O u MeO _N MeO NH ₂ HO N O O Step 1 H S O _O ^tBu O O tep 2 O ^OtBu Intermediate 6-A t _BuO ^O O ^t _BuO ^O O O O ^t Bu O NH t HO ₂ O ^t Bu BuO ^N _N O O ^t BuO ^N _N O O O O O N _N ^Ot Bu H ^t N _{N N} ^O Bu HO HBTU, DIPEA O N , DMF HO O O N H O O H O O ^OtBu O Step 3 O O ^t Bu Intermediate 6-B Intermediate 6-C NH.HCl ^t _BuO ^O O O ^t Bu tBuO ^N _N O O O H _{N N} ^Ot Bu O N N O O N HO O H N O O O ^OtBu N N N H OH Intermediate 1-C HO O N HBTU, DIPEA, DMF N Step 4 N N H OH Intermediate 6-D H _O ^O O OH HO ^N _N O O O H O N _{N N} ^OH N O O N H O O O ^{OH TFA:TIPS:H} _{2O 95:2.5:2.5} 37 °C HO O Step 5 N N O ^H N N H C ^{ompound F} Step 1: Synthesis of 4-(tert-Butyl) 1-methyl ((R)-5-(tert-butoxy)-5-oxo-4-(4,7,10-tris(2-(tert- butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)penta noyl)-L-aspartate (Intermediate 6-A) To a 20 mL scintillation vial with a stir bar was added (R)-DOTAGA( ^t Bu)4, (869 mg , 0.04 mmol, 1 equiv.), THF (25 mL) and DMF (5 mL). The reaction mixture was cooled to 0 °C and DIPEA (650 μL, 18.7 mg, 0.14 mmol, 3 equiv.), followed by HBTU, (719 mg, 0.04 mmol, 1.5 equiv.) was added and stirred for 5 min at 0 °C. The solution was brought to RT and stirred for 15 min and then 4-(tert-butyl) 1-methyl L-aspartate hydrochloride (300 mg, 0.04 mmol, 1 equiv.) was added as solid. The reaction was stirred at RT and was monitored by HPLC-MS. The reaction was stopped after 3h 30 min and solvent was evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 6-A (722 mg, 64%, purity: 98%) as white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.60 min; MS (positive ESI): found m/z 886.7 [M+H] ⁺ ; C ₄₄ H ₈₀ N ₅ O ₁₃ (calc. 886.6). ¹ H NMR (700 MHz, DMSO-d6) į 8.41 (s, 1H), 7.11 (s, 2H), 4.58 (q, J = 7.1 Hz, 1H), 4.06 (br s, 8H), 3.63 (s, 3H), 3.35 – 2.93 (m, 8H), 2.65 (dd, J = 16.1, 6.8 Hz, 2H), 2.56 – 2.49 (m, 2H), 1.87 (s, 2H), 1.52 – 1.40 (m, 36H), 1.39 (s, 9H). *Protons obscured by H2O and DMSO not reported. Step 2: Synthesis of (S)-4-(tert-Butoxy)-2-((R)-5-(tert-butoxy)-5-oxo-4-(4,7,10-t ris(2-(tert- butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)penta namido)-4-oxobutanoic acid (Intermediate 6-B): A flask containing Intermediate 6-A, (400.00 mg, 0.45 mmol, 1 equiv.) was dissolved in THF (6 mL) and water (3 mL) and placed in an ice bath and stirred for 15 min. Lithium hydroxide anhydrous (LiOH), (64.87 mg, 2.71 mmol, 6 equiv.) was added as a solid in one portion, and the reaction was continued in an ice-water bath. The reaction was monitored by HPLC-MS, after 30 min the major product was observed. After 1h, the reaction solution was acidified with Amberlite IR120 [H], ~600 mg by stirring for 15 min at rt, then filtered to remove the resin. The resin was further washed with acetonitrile, MeOH and the solvent was evaporated under vacuum. The crude product was lyophilized to give Intermediate 6-B as a white solid (394 mg, 95%, purity: 95%) and used for the next step without further purification. An aliquot was analyzed by HPLC- MS elution using elution method 2; retention time: 2.55 min; MS (positive ESI): found m/z 872.5 [M+H] ⁺ ; C43H78N5O13 (calc.872.6). ¹ H NMR (700 MHz, DMSO-d6) į 12.77 (br s, 1H), 8.24 (d, J = 8.2 Hz, 1H), 4.57 (td, J = 7.9, 5.9 Hz, 1H), 3.75 (s, 3H), 3.53 (s, 2H), 3.42 – 3.30 (m, 5H), 3.12 – 3.06 (m, 5H), 2.91 – 2.81 (m, 5H), 2.80 – 2.73 (m, 2H), 2.66 (dd, J = 15.9, 5.9 Hz, 1H), 2.54 – 2.48 (m, 2H), 2.23 – 2.13 (m, 2H), 1.93 – 1.85 (m, 1H), 1.82 – 1.75 (m, 1H), 1.48 – 1.41 (m, 36H), 1.39 (s, 9H). Step 3: Synthesis of (5R,10S)-10-(2-(tert-Butoxy)-2-oxoethyl)-2,2-dimethyl-4,8,11 -trioxo-5- (4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacy clododecan-1-yl)-3,15,18,21- tetraoxa-9,12-diazatetracosan-24-oic acid (Intermediate 6-C) To a 20 mL scintillation vial with a stir bar was added Intermediate 6-B, (70 mg, 0.08 mmol, 1 equiv.) and DMF (3 mL). The reaction mixture was cooled to 0 °C and DIPEA, (42 μL, 31.1 mg, 0.24 mmol, 3 equiv.), followed by HBTU, (31.1 mg, 0.08 mmol, 1.0 equiv.) was added and stirred for 10 min at 0 °C. The solution was brought to RT and stirred for 15 min and then 4- (tert-butyl) 3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)propanoic acid (19.7 mg, 0.08 mmol, 1 equiv.) was added as solid. The reaction was stirred at RT and was monitored by HPLC-MS. The reaction was stopped after 1h 45m and solvent was evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 6-C (70 mg, 66%, purity: 99%) as white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.40 min; MS (positive ESI): found m/z 1075.5 [M+H] ⁺ ; C ₅₂ H ₉₅ N ₆ O ₁₇ (calc. 1075.7). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C ₅₂ H ₉₅ N ₆ O ₁₇ 1075.6748; Found 1075.6750. ¹ H NMR (700 MHz, DMSO-d6) 8.12 (d, J = 8.4 Hz, 1H), 7.91 (br s, 1H), 7.08 (br s, 1H), 4.59 – 4.49 (m, 1H), 3.75 (s, 1H), 3.61 – 3.57 (m, 2H), 3.52 – 3.45 (m, 10H), 3.39 (dt, J = 6.1, 3.1 Hz, 3H), 3.27 – 3.20 (m, 2H), 3.20 – 3.12 (m, 3H), 3.12 – 3.02 (m, 3H), 2.91 – 2.72 (m, 2H), 2.61 (dd, J = 15.6, 5.4 Hz, 1H), 2.44 (t, J = 6.4 Hz, 2H), 2.41 – 2.29 (m, 1H), 1.93 – 1.70 (m, 2H), 1.50 – 1.39 (m, 36H), 1.38 – 1.36 (m, 9H). *Protons obscured by H2O and DMSO not reported. Step 4: Synthesis of (5R,10S)-10-(2-(tert-Butoxy)-2-oxoethyl)-2,2-dimethyl-4,8,11 -trioxo-5- (4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacy clododecan-1-yl)-3,15,18,21- tetraoxa-9,12-diazatetracosan-24-oic acid (Intermediate 6-D) To a 20 mL scintillation vial with a stir bar was added Intermediate 6-C (40 mg , 0.04 mmol, 1 equiv.) and 2.5 mL DMF. The reaction mixture cooled to 0 °C and DIPEA, (30.8 μL, 22.8 mg, 0.14 mmol, 4 equiv.), followed by HBTU, (13.7 mg, 0.04 mmol, 1 equiv.) was added and stirred for 5 min at 0 °C. The solution was brought to RT and stirred for 20 min and then Intermediate 1-C (17.9 mg, 0.04 mmol, 1 equiv.) was added as a solid. The reaction was stirred at RT and was monitored by HPLC-MS. The reaction was stopped after 75 min and solvent evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 6-D (36 mg, 57%, purity: 98%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.62 min; MS (positive ESI): found m/z 1520.9 [M+H] ⁺ ; C78H126N11O19 (calc.1520.9).HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C78H126N11O191520.9226; Found 1520.9172. ¹ H NMR (700 MHz, DMSO-d6) į 9.82 (br s, 2H), 8.95 (t, J = 5.9 Hz, 1H), 8.15 (br s, 1H), 7.93 (br s, 1H), 7.29 – 7.23 (m, 4H), 6.57 (s, 1H), 6.36 (s, 1H), 4.61 – 4.47 (m, 1H), 4.41 – 4.27 (m, 1H), 3.87 (d, J = 13.2 Hz, 1H), 3.79 – 3.65 (m, 10H), 3.63 – 3.59 (m, 8H), 3.54 – 3.47 (m, 11H), 3.39 (t, J = 6.1 Hz, 3H), 3.28 – 3.19 (m, 2H), 3.16 (qd, J = 7.1, 4.2 Hz, 3H), 3.08 (s, 1H), 2.97 – 2.80 (m, 4H), 2.61 – 2.51 (m, 6H), 2.49 – 2.43 (m, 3H), 1.81 – 1.73 (m, 2H), 1.68 – 1.56 (m, 2H), 1.50 – 1.39 (m, 36H), 1.37 (s, 9H), 1.21 – 1.08 (m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 1.00 (dd, J = 12.2, 4.2 Hz, 1H), 0.80 (d, J = 6.9 Hz, 6H). Step 5: Synthesis of 2,2',2''-(10-((15S,20R)-20-Carboxy-15-(carboxymethyl)-1-(4-( 4-(3-(2,4- dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-tri azol-4-yl)benzyl)piperidin-1-yl)- 1,14,17-trioxo-4,7,10-trioxa-13,16-diazaicosan-20-yl)-1,4,7, 10-tetraazacyclododecane-1,4,7- triyl)triacetic acid (Compound F) To a 20 mL scintillation vial with a stir bar was added Intermediate 6-D (46 mg, 0.03 mmol, 1 equiv.) and 2.5 mL of deprotection cocktail TFA:TIPS:H ₂ O - 95:2.5:2.5 (v/v/v) at RT. The reaction was brought to 37 °C by placing on a pre-heated oil bath at 37 °C and monitored by HPLC-MS. The reaction was stopped after 4h and reaction mixture placed under stream of air to remove TFA. The crude product was purified by preparative RP HPLC to afford Compound F (10.3 mg, 26 %, purity: 99%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 3.07 min; MS (positive ESI): found m/z 1240.3 [M+H] ⁺ ; C58H86N11O19 (calc.1240.6). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C58H86N11O191240.6096; Found 1240.6109. ¹ H NMR (700 MHz, DMSO-d6) į 10.65 (br s, 1H), 9.80 (br s, 1H), 8.94 (t, J = 5.9 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.89 (q, J = 6.0 Hz, 1H), 7.29 – 7.23 (m, 4H), 6.57 (s, 1H), 6.35 (s, 1H), 4.51 (dtd, J = 15.8, 7.9, 5.7 Hz, 2H), 4.36 (d, J = 13.0 Hz, 1H), 3.87 (d, J = 13.3 Hz, 1H), 3.61 (td, J = 6.7, 1.6 Hz, 2H), 3.52 – 3.47 (m, 20H), 3.42 – 3.35 (m, 2H), 3.28 – 3.19 (m, 1H), 3.19 – 3.11 (m, 6H), 3.09 (s, 1H), 2.96 – 2.86 (m, 5H), 2.65 – 2.57 (m, 2H), 2.55 (tt, J = 7.2, 3.6 Hz, 4H), 2.50 – 2.43 (m, 4H), 2.40 – 2.38 (m, 1H), 1.91 (s, 1H), 1.80 – 1.72 (m, 2H), 1.64 (d, J = 13.0 Hz, 1H), 1.59 (d, J = 12.7 Hz, 1H), 1.14 (qd, J = 12.6, 4.0 Hz, 2H), 1.03 (t, J = 7.2 Hz, 3H), 1.02 – 0.96 (m, 2H), 0.81 (d, J = 6.9 Hz, 6H). *4 exchangeable protons not observed. Example 7: Synthesis of (R)-2,2',2''-(10-(1-Carboxy-4-((2-(4-(4-(3-(2,4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-2- oxoethyl)amino)-4-oxobutyl)-1,4,7,10-tetraazacyclododecane-1 ,4,7-triyl)triacetic acid (Compound G) HO O O ^t Bu NH ₂ O ^t O OBu O O H O HO N N ^N _O ^t HO B _u ^{N N} _O ^t _Bu O HBTU, DIPEA, DMF O BuO ^{t t} N ^N BuO _N ^N O B ^uOt Step 1 O O ^BuOt O Intermediate 7-A NH.HCl O ^t O _O ^Bu H O N N HO O ^{N N} _O ^t _Bu N O N BuO ^t H _N ^N N N OH O termediate 1-C ^{B t} In ^uO _O HO O N HBTU, DIPEA, DMF N N N H OH S ^{tep 2} _{Intermediate 7-B} O O OH H O N N ^{N N} _OH O HO _N ^N TFA:TIPS:H O 95 O 2 :2.5:2.5 ^HO _O HO O 37 °C N N Step 3 N N H OH Compound G Step 1: Synthesis of (R)-(5-(tert-Butoxy)-5-oxo-4-(4,7,10-tris(2-(tert-butoxy)-2- oxoethyl)- 1,4,7,10-tetraazacyclododecan-1-yl)pentanoyl)glycine (Intermediate 7-A) To a 20 mL scintillation vial with a stir bar was added (R)-DOTAGA( ^t Bu)4 (462.2 mg , 0.66 mmol, 1 equiv.) and DMF (3 mL). The reaction mixture was cooled to 0 °C and DIPEA, (345μL, 256 mg, 1.98 mmol, 3 equiv.), followed by HBTU, (255mg, 0.66 mmol, 1 equiv.) was added and stirred for 10 min at 0 °C. The solution was brought to RT and stirred for 30 min and then glycine (50 mg, 0.66 mmol, 1 equiv.) was added as a solid. Glycine solubility was poor in reaction mixture, therefore TFA (0.3 mL) and pyridine (0.6 mL) were added to the reaction mixture and continued stirring at RT, pH ~5. The reaction was monitored by HPLC-MS. The reaction was stopped after 3h30m and solvent was evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 7-A (409 mg, 59%, purity: 95%) as white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 4.12 min; MS (positive ESI): found m/z 758.4 [M+H] ⁺ ; C ₃₇ H ₆₈ N ₅ O ₁₁ (calc. 758.5). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C ₃₇ H ₆₈ N ₅ O ₁₁ 758.4910; Found 758.4928. ¹ H NMR (700 MHz, DMSO-d6) į 8.28 (s, 1H), 7.10 (s, 1H), 4.51–3. 96 (m, 1H), 3.90 – 3.57 (m, 4H), 3.28 (s, 1H), 3.07 (s, 2H), 2.87 (s, 1H), 2.45 (s, 1H), 2.07 – 1.63 (m, 1H), 1.57 – 1.31 (m, 36H). *Protons obscured by H ₂ O and DMSO not reported. Step 2: Synthesis of tri-tert-Butyl 2,2’,2’’-(10-(1-(tert-butoxy)-5-((2-(4-(4-(3-(2,4-dihy droxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-2- oxoethyl)amino)-1,5-dioxopentan-2-yl)-1,4,7,10-tetraazacyclo dodecane-1,4,7-triyl)®-triacetate (Intermediate 7-B) To a 20 mL scintillation vial with a stir bar was added Intermediate 7-A (66.2 mg, 0.08 mmol, 1.4 equiv.) and DMF (3 mL). The reaction mixture was cooled to 0 °C and DIPEA, (51.7 μL, 38.4 mg, 0.3 mmol, 5 equiv.), followed by HBTU, (23 mg, 0.06 mmol, 1 equiv.) was added and stirred for 10 min at 0 °C. The solution was brought to RT and stirred for 15 min and then Intermediate 1-C (30 mg, 0.06 mmol, 1 equiv.) was added as a solid. The reaction was stirred at RT and monitored by HPLC-MS. Reaction was stopped after 2h and the solvent was evaporated under vacuum to give the crude product, which was purified by preparative RP HPLC to afford Intermediate 7-B (67 mg, 77%, purity: 98%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 5.21 min; MS (positive ESI): found m/z 1203.4 [M+H] ⁺ ; C ₆₃ H ₉₉ N ₁₀ O ₁₃ (calc.1203.7). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C63H99N10O131203.7388; Found 1203.7361. ¹ H NMR (700 MHz, DMSO-d6) į 9.84 (s, 1H), 8.96 (t, J = 5.9 Hz, 1H), 7.98 (s, 1H), 7.30 – 7.25 (m, 4H), 7.14 (s, 1H), 6.57 (s, 1H), 6.36 (s, 1H), 4.39 – 4.28 (m, 1H), 3.89 (s, 2H), 3.82 – 3.70 (m, 2H), 3.18 – 3.13 (m, 2H), 3.07 (s, 2H), 2.96 – 2.87 (m, 1H), 2.59 – 2.52 (m, 3H), 2.47 – 2.45 (m, 1H), 1.80 (t, J = 8.1 Hz, 1H), 1.64 (t, J = 15.6 Hz, 2H), 1.49 – 1.37 (m, 36H), 1.21 – 1.07 (m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 1.02 – 0.97 (m, 1H), 0.81 (d, J = 6.9 Hz, 6H). *Protons obscured by H ₂ O and DMSO not reported. Step 3: Synthesis of (R)-2,2',2''-(10-(1-Carboxy-4-((2-(4-(4-(3-(2,4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-2- oxoethyl)amino)-4-oxobutyl)-1,4,7,10-tetraazacyclododecane-1 ,4,7-triyl)triacetic acid (Compound G) To a 20 mL scintillation vial with a stir bar was added Intermediate 7-B (35 mg, 0.03 mmol) and 4 mL of deprotection cocktail TFA:TIPS:H ₂ O - 95:2.5:2.5 (v/v/v) at RT. The reaction was brought to 37 °C by placing on a pre-heated oil bath at 37 °C and monitored by HPLC-MS. The reaction was stopped after 3h and reaction mixture was placed under stream of air to remove TFA. The crude product was purified by preparative RP HPLC to afford Compound G (20 mg, 57 %, purity: 99%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 1.70 min; MS (positive ESI): found m/z 979.3 [M+H] ⁺ ; C44H62N10O11 (calc.979.4). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C44H62N10O11 979.4884; Found 979.4885. ¹ H NMR (700 MHz, DMSO-d6) į 10.62 (br s, 1H), 9.84 (br s, 1H), 8.95 (t, J = 6.0 Hz, 1H), 7.96 (br s, 1H), 7.28 – 7.25 (m, 4H), 6.57 (s, 1H), 6.36 (s, 1H), 4.34 – 4.30 (m, 1H), 4.07 (s, 1H), 3.91 (d, J = 5.6 Hz, 2H), 3.79 (d, J = 13.5 Hz, 2H), 3.50 (m, 13H), 3.16 (app. p, J = 7.0 Hz, 2H), 3.08 (s, 4H), 2.97 – 2.86 (m, 3H), 2.60 – 2.51 (m, 3H), 1.92 (br s, 2H), 1.83 – 1.75 (m, 1H), 1.64 (dd, J = 22.7, 12.9 Hz, 2H), 1.19 – 1.13 (m, 1H), 1.03 (t, J = 7.1 Hz, 3H), 1.02 – 0.97 (m, 1H), 0.81 (d, J = 6.9 Hz, 6H). *4 exchangeable protons not observed. Example 8: Synthesis of 2,2',2''-(10-((R)-1-Carboxy-4-(((S)-1-carboxy-4-(4-(4-(3-(2, 4- dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-tri azol-4-yl)benzyl)piperidin-1-yl)- 4-oxobutyl)amino)-4-oxobutyl)-1,4,7,10-tetraazacyclododecane -1,4,7-triyl)triacetic acid (Compound H)

O NH•HCl N O NHFmoc HO NHFmoc HBTU, DIPEA, DMF BuO ^t O HO O BuO ^t Step 1 HO O N O N N N N N H N H OH OH N Intermediate 1-C Intermediate 8-A O N O O ^t Bu NH ₂ HO O N N Piperidine, DMF O ^t Bu B ^uOt _O O BuO ^t N N Step 2 HO O N O B ^uOt N _O N N H OH Intermediate 8-B O N ^O _O ^t _Bu H N O N N O O ^t Bu HBTU, DIPEA, DMF ^BuOt _O BuO ^t N N HO O Step 3 O N BuO ^t N O N N H OH Intermediate 8-C O N ^O _OH H N O N N O OH TFA:TIPS:H ₂ O 95:2.5:2.5 HO O HO N N HO O 37 °C O N HO N O Step 4 N N H OH Compound H Step 1: Synthesis of tert-Butyl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-(4-(4-(3 - (2,4-dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2, 4-triazol-4-yl)benzyl)piperidin-1- yl)-5-oxopentanoate (Intermediate 8-A) To a 20 mL scintillation vial with a stir bar was added (S)-4-((((9H-fluoren-9- yl)methoxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid, (43 mg, 0.10 mmol, 1 equiv.) and DMF (3 mL). The reaction mixture was cooled to 0 °C and DIPEA, (70 μL, 51.7 mg, 0. 40 mmol, 4 equiv.), followed by HBTU, (38.7 mg, 0.10 mmol, 1 equiv.) was added and stirred for 15 min at 0 °C. The solution was brought to RT and stirred for 20 min and then Intermediate 1- C (50 mg, 0.10 mmol, 1 equiv.) was added as solid. The reaction was stirred at RT and monitored by HPLC-MS. The reaction was stopped after 2 h and solvent was evaporated under vacuum to give the crude product. The crude product was purified by RP chromatography to afford Intermediate 8-A (66 mg, 75%, purity: 98%) as a colorless film/solid. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 3.15 min; MS (positive ESI): found m/z 870.9 [M+H] ⁺ ; C ₅₀ H ₅₉ N ₆ O ₈ (calc.871.4). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C ₅₀ H ₅₉ N ₆ O ₈ 871.4389; Found 871.4396. ¹ H NMR (700 MHz, DMSO-d6) į 9.80 (br s, 1H), 8.96 (t, J = 5.9 Hz, 1H), 7.89 (t, J = 6.6 Hz, 2H), 7.73 (t, J = 7.0 Hz, 2H), 7.69 (dd, J = 8.0, 2.9 Hz, 1H), 7.42 (td, J = 7.5, 3.1 Hz, 2H), 7.35 – 7.31 (m, 2H), 7.30 – 7.19 (m, 4H), 6.58 (d, J = 4.1 Hz, 1H), 6.37 (d, J = 1.2 Hz, 1H), 4.39 – 4.21 (m, 4H), 4.00 – 3.92 (m, 1H), 3.79 (d, J = 13.0 Hz, 1H), 3.20 – 3.14 (m, 2H), 2.95 – 2.88 (m, 2H), 2.57 – 2.54 (m, 1H), 2.49 – 2.44 (m, 1H), 2.43 – 2.31 (m, 2H), 1.97 – 1.90 (m, 1H), 1.83 – 1.74 (m, 2H), 1.67 – 1.55 (m, 2H), 1.40 (s, 9H), 1.12 – 1.07 (m, 1H), 1.04 (t, J = 7.2 Hz, 3H), 0.99 (td, J = 12.4, 4.3 Hz, 1H), 0.82– 0.78 (m, 6H). *2 exchangeable protons not observed Step 2: Synthesis of tert-Butyl (S)-2-amino-5-(4-(4-(3-(2,4-dihydroxy-5-isopropylphenyl)-5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-5-oxopentanoate (Intermediate 8- B) To a 20 mL scintillation vial with a stir bar was added Intermediate 8-A, (60 mg, 0.07 mmol, 1 equiv.), followed by 6 mL of 15% piperidine solution in DMF at RT. The reaction was monitored by HPLC-MS. Reaction stopped after 1h and solvent was evaporated under vacuum to give the crude product. The product was obtained by precipitation with acetonitrile to afford Intermediate 8-B (37 mg, 67%, purity: 96%) as a colorless film/ solid. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.07 min; MS (positive ESI): found m/z 649.0 [M+H] ⁺ ; C35H49N6O6 (calc.649.4). Step 3: Synthesis of tri-tert-Butyl 2,2',2''-(10-((R)-1-(tert-butoxy)-5-(((S)-1-(tert-butoxy)-5- (4-(4- (3-(2,4-dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1 ,2,4-triazol-4- yl)benzyl)piperidin-1-yl)-1,5-dioxopentan-2-yl)amino)-1,5-di oxopentan-2-yl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetate (Intermediate 8-C): To a 20 mL scintillation vial with a stir bar was added (R)-5-(tert-butoxy)-5-oxo-4-(4,7,10-tris(2-(tert-butoxy)-2-o xoethyl)- 1,4,7,10-tetraazacyclododecan-1-yl)pentanoic acid, (16.5 mg, 0.02 mmol, 1 equiv.) and DMF (1.5 mL). Reaction mixture was cooled to 0 °C and DIPEA, (16.2 μL, 12 mg, 0.09 mmol, 4 equiv.), followed by HBTU, (9.2 mg, 0.02 mmol, 1 equiv.) was added and stirred for 15 min at 0 °C. The solution was brought to RT and stirred for 20 min and then Intermediate 8-B (18.5 mg, 0.02 mmol, 1 equiv.) was added as solution in DMF (0.5 mL). The reaction was stirred at RT and monitored by HPLC-MS. The reaction was stopped after 3h 30 min and the solvent was evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 8-C (24 mg, 64%, purity: 97%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 5.31 min; MS (positive ESI): found m/z 1331.8 [M+H] ⁺ ; C ₇₀ H ₁₁₁ N ₁₀ O ₁₅ (calc.1331.8). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C70H111N10O151331.8225; Found 1331.8283. ¹ H NMR (700 MHz, DMSO- d6) į 9.84 (br s, 1H), 8.96 (t, J = 5.9 Hz, 1H), 8.24 (br s, 1H), 7.31 – 7.25 (m, 4H), 7.10 (br s, 1H), 6.57 (s, 1H), 6.37 (d, J = 1.8 Hz, 1H), 4.37 (d, J = 12.9 Hz, 1H), 4.11 – 4.07 (m, 2H), 3.83 – 3.68 (m, 3H), 3.19 – 3.14 (m, 2H), 3.08 (s, 2H), 2.98 – 2.81 (m, 3H), 2.57 (d, J = 7.0 Hz, 2H), 2.50 – 2.45 (m, 1H), 2.43 (s, 1H), 2.37 – 2.31 (m, 2H), 1.91 – 1.86 (m, 2H), 1.82 – 1.76 (m, 3H), 1.68 – 1.60 (m, 2H), 1.49 – 1.42 (m, 36H), 1.40 (s, 9H), 1.11 (s, 1H), 1.04 (t, J = 7.2 Hz, 3H), 1.02 – 0.97 (m, 1H), 0.81 (d, J = 6.9 Hz, 6H). *Protons obscured by H ₂ O and DMSO not reported. Step 3: Synthesis of 2,2',2''-(10-((R)-1-Carboxy-4-(((S)-1-carboxy-4-(4-(4-(3-(2, 4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-4- oxobutyl)amino)-4-oxobutyl)-1,4,7,10-tetraazacyclododecane-1 ,4,7-triyl)triacetic acid (Compound H) To a 20 mL scintillation vial with a stir bar was added Intermediate 8-C (17 mg, 9.3 μmol, 1 equiv.) and 2.5 mL of deprotection cocktail TFA:TIPS:H2O - 95:2.5:2.5 (v/v/v) at RT. The reaction was brought to 37 °C by placing on a pre-heated oil bath at 37 °C and monitored by HPLC-MS. The reaction was stopped after 2h30 min and the reaction mixture was placed under stream of air to remove TFA. The crude product was purified by preparative RP HPLC to afford Compound H (10.5 mg, 87 %, purity: 99%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 1.71 min; MS (positive ESI): found m/z 1051.6 [M+H] ⁺ ; C ₅₀ H ₇₁ N ₁₀ O ₁₅ (calc.1051.5). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C ₅₀ H ₇₁ N ₁₀ O ₁₅ 1051.5095; Found 1051.5125. ¹ H NMR (700 MHz, DMSO-d6) į 9.82 (s, 1H), 8.95 (t, J = 5.9 Hz, 1H), 8.19 (d, J = 7.5 Hz, 1H), 7.27 (d, J = 1.6 Hz, 4H), 6.57 (s, 1H), 6.36 (s, 1H), 4.38 – 4.34 (m, 1H), 4.20 – 4.16 (m, 1H), 3.80 (d, J = 13.5 Hz, 1H), 3.18 – 3.13 (m, 2H), 2.97 – 2.86 (m, 3H), 2.62 – 2.52 (m, 2H), 2.49 – 2.41 (m, 5H), 2.40 – 2.32 (m, 2H), 1.96 – 1.89 (m, 3H), 1.84 – 1.76 (m, 1H), 1.66 (d, J = 12.5 Hz, 1H), 1.59 (d, J = 12.8 Hz, 1H), 1.18 – 1.09 (m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 1.02 – 0.98 (m, 1H), 0.81 (d, J = 6.9 Hz, 6H). *Protons obscured by H ₂ O and DMSO not reported. Example 9: Synthesis of 2,2',2''-(10-((R)-1-Carboxy-4-(((S)-4-carboxy-1-((2-(4-(4-(3 -(2,4- dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-tri azol-4-yl)benzyl)piperidin-1-yl)- 2-oxoethyl)amino)-1-oxobutan-2-yl)amino)-4-oxobutyl)-1,4,7,1 0-tetraazacyclododecane-1,4,7- triyl)triacetic acid (Compound I) O O ^t Bu t _B ^{O O t} O _uO t B B _u ^O O ^t _BuO O O u O _O NH ₂ O O ^t Bu O tBuO ^N _N O ^N _N LiOH tBuO ^N _N HBTU, DIPEA, DMF ^t BuO O O ^Ot Bu O _O HO ^N _N N ^Ot Bu ^THF:H ₂ N N _N ^Ot Bu O N _N H O O HO H Step O O ^t Bu O O 2 O ^Ot O B ^u Step 1 O O ^t Bu Intermediate 9-A Intermediate 9-B NH•HCl O O NHFmoc BnO O N NH N ₂ N N N N H OBn Intermediate 2-B BnO O O O N Piperidine, DMF BnO HBTU, DIPEA, DMF N NHFmoc N HO N N H Step N OBn 4 N N H Step 3 OBn I _{ntermediate 9-C} ^{Intermediate 9-D t O t} _BuO O OBu O tBuO ^N _N O Intermediate 9-B _H ^O N ^{N Ot} Bu N N _N H HBTU, DIPEA, DMF O O O O ^t Bu Step 5 Intermediate 9-D BnO O N N N N H O ^Bn _{Intermediate 9-E} t ^{O O} _{BuO O} ^t _Bu O t _BuO ^N _N O H ^O N ^N _N ^Ot _Bu N N H P _{d/C, H2} ^O O O _O ^t _Bu Step 6 HO O N N N N H O ^H _{Intermediate 9-F OH} ^HO O O _O HO ^N _N O H ^O N N ^OH N N _N H O O TFA:TIPS:H ₂ O 95:2.5:2.5 O OH 37 °C Step 7 HO O N N N N H OH Compound I Step 1: Synthesis of 5-(tert-Butyl) 1-methyl ((R)-5-(tert-butoxy)-5-oxo-4-(4,7,10-tris(2-(tert- butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)penta noyl)-L-glutamate (Intermediate 9-A) To a 20 mL scintillation vial with a stir bar was added (R)-DOTAGA( ^t Bu)4 (350 mg, 0.5 mmol, 1 equiv.) and 7 mL DMF. The reaction mixture was cooled to 0 °C and DIPEA, (348 μL, 258 mg, 2 mmol, 4 equiv.), followed by HBTU, (208mg, 0.55 mmol, 1.1 equiv.) was added and stirred for 10 min at 0 °C. The solution was brought to RT and was stirred for 15 min and then 5- (tert-butyl) 1-methyl L-glutamate HCl (127 mg, 0.5 mmol, 1 equiv.) was added as a solid. The reaction was stirred at RT and was monitored by HPLC-MS. The reaction was stopped after 2 h and the solvent was evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 9-A (412 mg, 71%, purity: 97%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.67 min; MS (positive ESI): found m/z 900.4 [M+H] ⁺ ; C45H82N5O13 (calc. 900.6). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C ₄₅ H ₈₂ N ₅ O ₁₃ 900.5904; Found 900.5936. ¹ H NMR (700 MHz, DMSO-d6) į 8.32 (s, 1H), 7.05 (s, 1H), 4.35 (s, 1H), 4.24 – 4.19 (m, 1H), 3.62 (s, 3H), 3.28 (s, 3H), 3.07 (s, 2H), 2.58 – 2.51 (m, 1H), 2.45 (s, 1H), 2.25 (t, J = 7.6 Hz, 2H), 1.94 – 1.86 (m, 1H), 1.82 – 1.74 (m, 1H), 1.52 – 1.40 (m, 36H), 1.39 (s, 9H). *Protons obscured by H ₂ O and DMSO not reported. Step 2: Synthesis of (S)-5-(tert-Butoxy)-2-((R)-5-(tert-butoxy)-5-oxo-4-(4,7,10-t ris(2-(tert- butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)penta namido)-5-oxopentanoic acid (Intermediate 9-B) To a flask containing 5-(tert-Butyl) 1-methyl ((R)-5-(tert-butoxy)-5-oxo-4-(4,7,10-tris(2-(tert- butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)penta noyl)-L-glutamate (Intermediate 9-A) (164mg, 0.18 mmol, 1 equiv.) was dissolved in THF (5 mL) and water (2.5 mL) and placed in an ice bath and stirred for 10 min. Lithium hydroxide anhydrous (LiOH), (21.8 mg, 0.91 mmol, 5 equiv.) was added as a solid in one portion and thereaction was stirredin an ice-water bath. The reaction was monitored by HPLC-MS, after 1h was worked up by acidification with Amberlite IR120 [H], at rt to pH ~5, then filtered via a 0.2 μM filter disk to remove resin. The resin was further washed with ACN, MeOH and the solvent was evaporated under vacuum. The crude product was dissolved in acetonitrile/water and lyophilised to give Intermediate 9-B (159 mg, 94%, purity: 95%) as a white solid. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.57 min; MS (positive ESI): found m/z 886.3 [M+H] ⁺ ; C44H80N5O13 (calc. 886.6). Step 3: Synthesis of (9H-Fluoren-9-yl)methyl (2-(4-(4-(3-(2,4-bis(benzyloxy)-5-isopropylphenyl)- 5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1- yl)-2-oxoethyl)carbamate (Intermediate 9-C) To a 20 mL scintillation vial with a stir bar was added (((9H-fluoren-9- yl)methoxy)carbonyl)glycine, (24.4 mg, 0.08 mmol, 1 equiv.) and DMF (1.5 mL). The reaction mixture was cooled to 0 °C and DIPEA, (28 μL, 0.16 mmol, 2 equiv.), followed by HBTU, (31.4 mg, 0.08 mmol, 1 equiv.) was added and stirred for 5 min at 0 °C. The solution was brought to RT and stirred for 20 min and then solution of Intermediate 2-B (55 mg, 0.08 mmol, 1 equiv.) in DMF (1.5 mL) containing DIPEA, (53 μL, 0.24 mmol, 3 equiv.) was added. The reaction was stirred at RT and was monitored by HPLC-MS. The reaction was stopped after 1h 30 min and solvent was evaporated under vacuum to give the crude product, which was purified by normal phase chromatography to afford Intermediate 9-C (58 mg, 76%, purity: 98%) as a white solid. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 3.48 min; MS (positive ESI): found m/z 923.1 [M+H] ⁺ ; C57H59N6O6 (calc.923.5). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C57H59N6O6923.4491; Found 923.4525. ¹ H NMR (700 MHz, DMSO-d6) į 8.97 (t, J = 5.9 Hz, 1H), 7.90 (d, J = 7.5 Hz, 2H), 7.72 (d, J = 7.5 Hz, 2H), 7.44 – 7.30 (m, 13H), 7.25 (d, J = 7.4 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 7.05 (s, 1H), 6.98 (d, J = 8.0 Hz, 2H), 6.77 (s, 1H), 5.08 (s, 2H), 4.94 (s, 2H), 4.33 – 4.21 (m, 4H), 3.83 (qd, J = 16.7, 5.9 Hz, 2H), 3.78 – 3.72 (m, 1H), 3.66 – 3.59 (m, 1H), 3.18 (q, J = 6.9 Hz, 2H), 3.13 – 3.08 (m, 1H), 2.92 – 2.86 (m, 1H), 2.69 (s, 1H), 2.49 – 2.47 (m, 1H), 1.77 – 1.69 (m, 1H), 1.52 (dd, J = 22.9, 13.0 Hz, 2H), 1.27 – 1.25 (m, 2H), 1.05 (t, J = 7.2 Hz, 3H), 1.03 (d, J = 6.9 Hz, 6H). Step 4: Synthesis of 5-(2,4-bis(Benzyloxy)-5-isopropylphenyl)-N-ethyl-4-(4-((1-gl ycylpiperidin-4- yl)methyl)phenyl)-4H-1,2,4-triazole-3-carboxamide (Intermediate 9-D) Piperidine (0.45 mL) was added to a solution of (9H-fluoren-9-yl)methyl (2-(4-(4-(3-(2,4- bis(benzyloxy)-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2, 4-triazol-4-yl)benzyl)piperidin-1- yl)-2-oxoethyl)carbamate (Intermediate 9-C), ( 50 mg, 0.05 mmol, 1 equiv) in DMF (2.55 mL) and the mixture stirred at RT. The reaction was monitored by HPLC-MS and after 1h at RT the reaction stopped. The solvent was evaporated under vacuum and the crude product was purified by RP chromatography to give Intermediate 9-D (24.6 mg, 64%, purity 98%) as a white solid. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.48 min; MS (positive ESI): found m/z 701.1 [M+H] ⁺ ; C42H49N6O4 (calc.701.4). Step 5: Synthesis of tri-tert-Butyl 2,2',2''-(10-((R)-5-(((S)-1-((2-(4-(4-(3-(2,4-bis(benzyloxy) -5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-2- oxoethyl)amino)-5-(tert-butoxy)-1,5-dioxopentan-2-yl)amino)- 1-(tert-butoxy)-1,5-dioxopentan-2- yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Intermediate 9-E) To a 20 mL scintillation vial with a stir bar was added Intermediate 9-B (22.8 mg, 0.02 mmol, 1 equiv.) and DMF (2 mL). The reaction mixture was cooled to 0 °C and DIPEA, (19 μL, 14.2 mg, 0.11 mmol, 4.5 equiv.), followed by HBTU(9.4 mg, 0.02 mmol, 1 equiv.) was added and stirred for 15 min at 0 °C. The solution was brought to RT and stirred for 20 min and then Intermediate 9-D (18 mg, 0.02 mmol, 1 equiv.) was added dissolved in DMF (1 mL). The reaction was stirred at RT and was monitored by HPLC-MS. The reaction was stopped after 1 h 45 min and the solvent was evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 9-E (30 mg, 65%, purity: 95%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 3.12 min; MS (positive ESI): found m/z 1569.5 [M+H] ⁺ ; C86H126N11O16 (calc.1568.9). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C86H126N11O161568.9379; Found 1568.9403. ¹ H NMR (700 MHz, DMSO-d6) į 8.98 (td, J = 6.0, 2.2 Hz, 1H), 7.92 (s, 1H), 7.41 – 7.36 (m, 4H), 7.36 (t, J = 7.4 Hz, 2H), 7.35 – 7.29 (m, 2H), 7.27 – 7.23 (m, 2H), 7.10 – 7.06 (m, 2H), 7.03 (d, J = 2.4 Hz, 1H), 7.01 – 6.97 (m, 2H), 6.77 (s, 1H), 5.08 (s, 2H), 4.95 (d, J = 3.3 Hz, 2H), 4.31 – 4.29 (m, 2H), 4.00 – 3.81 (m, 2H), 3.74 (d, J = 13.6 Hz, 2H), 3.22 – 3.14 (m, 2H), 3.13 – 3.06 (m, 2H), 2.96 – 2.85 (m, 1H), 2.49 – 2.48 (m, 4H), 2.28 – 2.20 (m, 2H), 1.92 – 1.84 (m, 1H), 1.77 – 1.69 (m, 3H), 1.47 – 1.40 (m, 36H), 1.38 (s, 9H), 1.05 (t, J = 7.2 Hz, 3H), 1.01 (dd, J = 6.9, 2.0 Hz, 6H). *Protons obscured by H2O and DMSO not reported. Step 6: Synthesis of tri-tert-Butyl 2,2',2''-(10-((R)-1-(tert-butoxy)-5-(((S)-5-(tert-butoxy)-1- ((2-(4- (4-(3-(2,4-dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4 H-1,2,4-triazol-4- yl)benzyl)piperidin-1-yl)-2-oxoethyl)amino)-1,5-dioxopentan- 2-yl)amino)-1,5-dioxopentan-2-yl)- 1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Intermediate 9-F) To a flask containing Intermediate 9-E (26 mg, 16.6 μmol, 1 equiv.) and methanol (5 mL) was added 10% Pd/C (3.4 mg, 3.32 μmol, 0.2 equiv.) at room temperature. The reaction mixture was degassed under vacuum and subjected to hydrogen gas via a balloon. The reaction was stirred overnight and was monitored by HPLC-MS. The reaction was stopped after 15 hours, filtered through 0.2 μM filter disk and solvent evaporated under vacuum to give the crude Intermediate 9-F (22 mg, 86 %, purity: 90%) as colorless film, which was used for next step without further purification. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.73 min; MS (positive ESI): found m/z 1389.4 [M+H] ⁺ ; C ₇₂ H ₁₁₄ N ₁₁ O ₁₈ (calc. 1388.8). Step 7: Synthesis of 2,2',2''-(10-((R)-1-Carboxy-4-(((S)-4-carboxy-1-((2-(4-(4-(3 -(2,4-dihydroxy- 5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl) benzyl)piperidin-1-yl)-2- oxoethyl)amino)-1-oxobutan-2-yl)amino)-4-oxobutyl)-1,4,7,10- tetraazacyclododecane-1,4,7- triyl)triacetic acid (Compound I) To a 20 mL scintillation vial with a stir bar was added Intermediate 9-F (22 mg, 15.68 μmol) and 2.5 mL of deprotection cocktail TFA:TIPS:H2O - 95:2.5:2.5 (v/v/v) at RT. The reaction was brought to 37 °C by placing on a pre-heated oil bath at 37 °C and was monitored by HPLC-MS. The reaction was stopped after 4h and the reaction mixture was placed under stream of air to remove TFA. The crude product was purified by preparative RP HPLC to afford Compound I (5 mg, 23 %, purity: 97%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 2.84 min; MS (positive ESI): found m/z 1108.5 [M+H] ⁺ ; C ₅₂ H ₇₄ N ₁₁ O ₁₆ (calc.1108.5). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C52H74N11O161108.5310; Found 1108.5332. ¹ H NMR (700 MHz, DMSO-d6) į 10.65 (s, 1H), 9.79 (s, 1H), 8.95 (td, J = 5.9, 2.4 Hz, 1H), 8.09 (d, J = 9.2 Hz, 1H), 7.95 – 7.91 (m, 1H), 7.28 – 7.26 (m, 3H), 6.57 (d, J = 1.9 Hz, 1H), 6.35 (s, 1H), 4.34 – 4.28 (m, 2H), 4.04 – 3.84 (m, 1H), 3.77 (d, J = 13.5 Hz, 1H), 3.19 – 3.13 (m, 2H), 3.09 (s, 2H), 2.97 – 2.86 (m, 3H), 2.58 – 2.52 (m, 3H), 2.44 (s, 2H), 2.32 – 2.26 (m, 2H), 1.94 – 1.87 (m, 3H), 1.81 – 1.71 (m, 1H), 1.65 – 1.60 (m, 2H), 1.18 – 1.14 (m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 0.81 (d, J = 6.9 Hz, 6H). *Protons obscured by H ₂ O and DMSO not reported. Example 10: Synthesis of 2,2',2''-(10-(2-(((S)-1-(((S)-1-(((S)-5-Amino-1-(4-(4-(3-(2, 4- dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-tri azol-4-yl)benzyl)piperidin-1-yl)- 1,5-dioxopentan-2-yl)amino)-4-carboxy-1-oxobutan-2-yl)amino) -5-guanidino-1-oxopentan-2- yl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-t riyl)triacetic acid (Compound J) NH •HCl BnO O N ^t BuO O N O t ^BuO _O N N H ^t BuO O OBn O O tBuO H H O O Intermediate 2-B N N N N N N ^t SPPS H H HBTU, DIPEA H OBu N N N O O Cl HO N N N H _O ^tBu N O Cl O O N DMF, RT HN HN Step 1 N O O Step 2 Trt O ^t Bu HN O HN t BnO O HN NH O Trt OBu N Pbf HN NH O N Pbf H OBn N N I ^{ntermediate 10-A} _{Intermediate 10-B} HO O O HO O O H H N N N N N N H OH 1 _{) Pd/C, H2} ^{, MeOH, RT} O O N N O 2 _{) TFA/TIPS/H2} ^{O 95:2.5:2.5} 37 °C ^H ₂ ^{N O} HN OH H _O ^{O H} ₂ ^{N NH} O N Step 3 N N H Compound J OH N Step 1: Synthesis of N ² -((S)-5-(tert-Butoxy)-5-oxo-2-((S)-5-(3-((2,2,4,6,7-pe ntamethyl-2,3- dihydrobenzofuran-5-yl)sulfonyl)guanidino)-2-(2-(4,7,10-tris (2-(tert-butoxy)-2-oxoethyl)- 1,4,7,10-tetraazacyclododecan-1-yl)acetamido)pentanamido)pen tanoyl)-N ⁵ -trityl-L-glutamine (Intermediate 10-A) The protected peptide was synthesized by solid phase peptide synthesis (SPPS) on 2- chlorotritylchloride resin (Chem-Impex, 0.72 mmol/g, 139 mg, 0.1 mmol). Fmoc-Gln(Trt)-OH (305 mg, 0.5 mmol) was dissolved in DMF (4 mL) with potassium iodide (16 mg, 0.1 mmol) and DIPEA (174 μL, 1.0 mmol). The resulting solution was combined with the resin and stirred at room temperature overnight. Fmoc deprotection was performed for 5 and 15 minutes with 20% piperidine in DMF. Subsequent couplings were performed using 0.3 mmol of protected amino acids (Fmoc-Glu(OtBu)-OH, Fmoc-Arg(Pbf)-OH and DOTA(OtBu)3) 0.3 mmol of HBTU and 0.6 mmol of DIPEA in DMF for 1 hour. Couplings were monitored by Kaiser test. After the final coupling, the resin was washed thoroughly with DCM. Cleavage from resin was performed with 20% HFIP in DCM (5 mL) for 30 minutes. The resin was drained and washed with DCM (2 mL), and the combined washings were concentrated under a stream of air. The resulting crude protected peptide was dissolved in DMSO and purified by preparative RP HPLC. Purified protected peptide Intermediate 10-A was obtained as a colourless solid after lyophilization (38.5 mg, 25%, purity: 98%). An aliquot was analyzed by HPLC-MS using elution method 4; retention time: 4.98 min; MS (ESI+) m/z calculated for C ₈₀ H ₁₁₈ N ₁₁ O ₁₇ S [M+H] ⁺ 1536.8; found 1536.9. ¹ H NMR (700 MHz, DMSO-d ₆ ^^į^^^^^^^V^^^+^^^^^^^^^V^^^+^^^^^^^^^V^^^+^^^^^^^^^V ^^^+^^^ 7.31 (s, 1H), 7.28 – 7.24 (m, 7H), 7.21 – 7.18 (m, 3H), 7.17 – 7.15 (m, 7H), 6.68 (s, 1H), 6.37 (s, 1H), 4.35 – 4.29 (m, 1H), 4.26 (s, 1H), 4.22 – 4.12 (m, 2H), 4.12 – 4.01 (m, 1H), 3.92 (s, 1H), 3.60 – 3.43 (m, 5H), 3.36 (s, 3H), 3.32 – 3.19 (m, 3H), 3.19 – 3.09 (m, 2H), 3.08 – 2.97 (m, 4H), 2.95 (s, 3H), 2.89 (s, 2H), 2.81 (d, J = 26.0 Hz, 1H), 2.47 (s, 3H), 2.41 (s, 3H), 2.39 – 2.34 (m, 2H), 2.24 (t, J = 8.5 Hz, 2H), 2.07 (s, 1H), 2.00 (s, 3H), 1.93 – 1.85 (m, 2H), 1.79 – 1.73 (m, 2H), 1.73 – 1.66 (m, 1H), 1.47 (s, 9H), 1.40 (s, 9H), 1.38 (m, 27H). Step 2: Synthesis of tri-tert-Butyl 2,2',2''-(10-((6S,9S,12S)-6-(4-(4-(3-(2,4-bis(benzyloxy)-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidine-1-carbonyl)-9-(3- (tert-butoxy)-3-oxopropyl)-3,8,11,14-tetraoxo-12-(3-(3-((2,2 ,4,6,7-pentamethyl-2,3- dihydrobenzofuran-5-yl)sulfonyl)guanidino)propyl)-1,1,1-trip henyl-2,7,10,13- tetraazapentadecan-15-yl)-1,4,7,10-tetraazacyclododecane-1,4 ,7-triyl)triacetate (Intermediate 10-B) Intermediate 10-A (21 mg, 0.02 mmol), Intermediate 2-B (15 mg, 0.022 mmol), HBTU (7.6 mg, 0.02 mmol) and DIPEA (18 μL, 0.1 mmol) were dissolved in DMF (2 mL) and stirred for 1 hour at room temperature. The solvent was evaporated under reduced pressure and the residue redissolved in DMSO (<1 mL). The crude product was purified by preparative RP HPLC to give Intermediate 10-B as a colourless solid after lyophilization (23 mg, 54%, purity: 98%). An aliquot was analyzed by HPLC-MS using elution method 4; retention time: 6.15 min; MS (ESI+) m/z calculated for C120H162N16O19S [M+2H] ²⁺ 1082.1; found 1082.3. Step 3: Synthesis of 2,2',2''-(10-(2-(((S)-1-(((S)-1-(((S)-5-Amino-1-(4-(4-(3-(2, 4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-1,5- dioxopentan-2-yl)amino)-4-carboxy-1-oxobutan-2-yl)amino)-5-g uanidino-1-oxopentan-2- yl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-t riyl)triacetic acid (Compound J) 10% w/w Palladium on carbon (30% w/w, 3.5 mg) was added to a 5 mL microwave vial with a stir bar and sealed with a septum and crimp cap. The vial was purged with nitrogen, followed by the addition of Intermediate 10-B (23 mg, 10.8 μmol) dissolved in methanol (2 mL). The vial was then purged with hydrogen and a hydrogen balloon attached to the vial. After stirring for 2 hours at room temperature, the vial was purged with nitrogen and the vial unsealed. The reaction mixture was filtered through a 0.2 μm syringe filter and the solvent evaporated under reduced pressure. The resulting product was dissolved in 2 mL of 95:2.5:2.5 TFA/ /TIPS/H2O (v/v/v) and stirred at 37 °C in a heating block for 90 minutes. The solvent was then evaporated under a stream of air and the resulting crude product redissolved in DMSO, filtered through a 0.2 μm syringe filter and purified by preparative RP HPLC. Compound J was obtained as a colourless solid after lyophilization (5.9 mg, 34%, purity: 99%) as the TFA salt. An aliquot was analyzed by HPLC-MS using elution method 4; retention time: 4.53 min; HRMS (ESI+) m/z calculated for C ₅₈ H ₈₈ N ₁₆ O ₁₆ [M+2H] ²⁺ 632.3277; found 632.3268. ¹ H NMR (700 MHz, DMSO-d ₆ ^^į^^^^^^^V^^ 1H), 8.96 (t, J = 5.4 Hz, 1H), 8.71 (s, 1H), 8.27 – 8.03 (m, 2H), 7.81 (s, 1H), 7.29 – 7.25 (m, 4H), 7.25 (m, 1H), 6.82 (m, 1H), 6.57 (s, 1H), 6.36 (s, 1H), 4.79 – 4.67 (m, 2H), 4.43 – 4.32 (m, 4H), 4.32 – 4.28 (m, 1H), 4.27 – 4.22 (m, 1H), 4.12 – 3.88 (m, 9H), 3.71 – 3.52 (m, 4H), 3.47 – 3.24 (m, 7H), 3.19 – 3.15 (m, 2H), 3.13 – 3.02 (m, 8H), 3.02 – 2.93 (m, 1H), 2.90 (h, J = 6.7 Hz, 1H), 2.32 – 2.20 (m, 2H), 2.20 – 2.00 (m, 2H), 1.97 – 1.82 (m, 2H), 1.81 – 1.68 (m, 3H), 1.68 – 1.59 (m, 3H), 1.59 – 1.45 (m, 3H), 1.03 (t, J = 7.2 Hz, 3H), 0.81 (d, J = 6.7 Hz, 6H). * 9 exchangeable protons not observed. Example 11: Synthesis of (S)-2,2',2''-(10-(1-Carboxy-4-((2-(4-(4-(3-(2,4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidine-1- carboxamido)ethyl)amino)-4-oxobutyl)-1,4,7,10-tetraazacyclod odecane-1,4,7-triyl)triacetic acid (Compound K) O O ^t Bu O H O t _BuO ^O N O N N _N ^N O ^t Bu -NO-Phenyl chl ^H O tBuO ^N _N 1. p ₂ oroformate ^t BuO N ^N O ^t DIPEA, THF Bu H ₂ N _{N N} ^O O N ^tBuO H O NH•HCl _O Bn O O ^t O O ^Bu 2. N N N N H Intermediate 5-A OBn Intermediate 11-A BnO O N N N N H OBn Intermediate 2-B Step 1 O O ^t Bu O H O N N N _N ^N H O ^t Bu O Pd/C, H ₂ BuO ^t N ^N Step 2 O B ^uOt O HO O N N N N H OH Intermediate-11-B O OH O H O N N N _N ^N H OH O HO N ^N TFA:TIPS:H ₂ O 95:2.5:2.5 O H ^O 37 °C _O HO O N Step 3 N N N H OH Compound K Step 1: Synthesis of tri-tert-Butyl 2,2',2''-(10-(5-((2-(4-(4-(3-(2,4-bis(benzyloxy)-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidine-1- carboxamido)ethyl)amino)-1-(tert-butoxy)-1,5-dioxopentan-2-y l)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)(S)-triacetate (Intermediate 11-A) To a solution of tri-tert-butyl 2,2',2''-(10-(5-((2-aminoethyl)amino)-1-(tert-butoxy)-1,5- dioxopentan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl )(R)-triacetate (Intermediate 5-A) (50 mg, 0.06 mmol, 1 equiv.) in anhydrous THF (4 mL) and stir bar was added DIPEA (32 μL, 0.18 mmol, 3 equiv.) and cooled to 0 °C, followed by addition of 4-nitrophenylchloroformate (12.7 mg, 0.06 mmol, 1 equiv.) at 0 °C in one portion. The reaction was initially stirred at 0 °C for 20 min., after which was brought to RT and was monitored by HPLC-MS. After 30 min at RT complete conversion to the nitrophenyl intermediate was observed by HPLC-MS. Added Intermediate 2-B (59 mg, 0.08 mmol, 1.4 equiv.) as a solid to the reaction and continued stirring at RT. After 1h additional Intermediate 2-B (26 mg, 0.04 mmol, 0.6 equiv.), followed by DIPEA (32 μL, 0.18 mmol, 3 equiv.) was added^^7KH^UHDFWLRQ^PL[WXUH^ZDV^EURXJKW^WR^^^^^^ and stirring was continued overnight. $IWHU^^^^K^DW^^^^^^^WKH^UHDFWLRQ^ZDV^VWRSSHG^E\^DGGLQJ^ methanol and stirring for 10 min at RT. The reaction mixture was concentrated under vacuum, followed by RP chromatography to afford Intermediate 11-A (34 mg, 40%, purity: 95%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.92 min; MS (positive ESI): found m/z 1412.5 [M+H] ⁺ ; C ₇₈ H ₁₁₄ N ₁₁ O ₁₃ (calc. 1412.9). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C ₇₈ H ₁₁₄ N ₁₁ O ₁₃ 1412.8592; Found 1412.8552. ¹ H NMR (700 MHz, DMSO-d6) į 8.99 (t, J = 5.9 Hz, 1H), 7.96 (br s, 1H), 7.42 – 7.34 (m, 6H), 7.36 – 7.30 (m, 2H), 7.28 – 7.24 (m, 2H), 7.11 – 7.06 (m, 4H), 7.03 (s, 1H), 6.99 (d, J = 8.0 Hz, 2H), 6.78 (s, 1H), 6.51 (t, J = 5.5 Hz, 1H), 5.09 (s, 2H), 4.96 (s, 2H), 4.43 – 3.94 (m, 1H), 3.89 (d, J = 12.8 Hz, 2H), 3.20 – 3.15 (m, 2H), 3.14 – 2.98 (m, 7H), 2.56 (t, J = 12.5 Hz, 2H), 2.48 (d, J = 7.1 Hz, 2H), 1.51 – 1.39 (m, 40H), 1.05 (t, J = 7.2 Hz, 3H), 1.01 (d, J = 6.9 Hz, 6H). *Protons obscured by H ₂ O and DMSO not reported. Step 2: Synthesis of tri-tert-Butyl 2,2',2''-(10-(1-(tert-butoxy)-5-((2-(4-(4-(3-(2,4-dihydroxy- 5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidine-1- carboxamido)ethyl)amino)-1,5-dioxopentan-2-yl)-1,4,7,10-tetr aazacyclododecane-1,4,7- triyl)(S)-triacetate (Intermediate 11-B) To a flask containing Intermediate 11-A (30 mg, 19.11 μmol) and methanol (4.5 mL) was added 10% Pd/C (8 mg, 7.64 μmol, 0.4 equiv.) at room temperature. The reaction mixture was degassed under vacuum and subjected to hydrogen gas via a balloon. The reaction was stirred overnight and was monitored by HPLC-MS. The reaction was stopped after 15 hours, filtered through a 0.2 μM filter disk and solvent evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 11-B (18.4 mg, 66 %, purity: 98%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 4.78 min; MS (positive ESI): found m/z 1232.5 [M+H] ⁺ ; C64H102N11O13 (calc.1232.8). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C64H102N11O13 1232.7680; Found 1232.7680. ¹ H NMR (700 MHz, DMSO-d6) į 9.82 (br s, 1H), 8.96 (t, J = 5.9 Hz, 1H), 7.31 – 7.25 (m, 4H), 7.11 (s, 2H), 6.57 (s, 1H), 6.54 (br s, 1H), 6.37 (s, 1H), 3.92 (d, J = 13.4 Hz, 2H), 3.20 – 3.13 (m, 2H), 3.10 – 3.01 (m, 8H), 2.94 – 2.87 (m, 1H), 2.61 – 2.54 (m, 4H), 2.47 – 2.39 (m, 2H), 1.72 – 1.65 (m, 1H), 1.57 (d, J = 12.6 Hz, 2H), 1.51 – 1.37 (m, 38H), 1.09 – 1.05 (m, 1H), 1.04 (t, J = 7.2 Hz, 3H), 0.80 (d, J = 6.0 Hz, 6H). *Protons obscured by H2O and DMSO not reported. Step 3: Synthesis of (S)-2,2',2''-(10-(1-Carboxy-4-((2-(4-(4-(3-(2,4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidine-1- carboxamido)ethyl)amino)-4-oxobutyl)-1,4,7,10-tetraazacyclod odecane-1,4,7-triyl)triacetic acid (Compound K) To a 20 mL scintillation vial with a stir bar was added Intermediate 11-B (18 mg, 10.73 μmol, 1 equiv.) and 2.5 mL of deprotection cocktail TFA:TIPS:H ₂ O - 95:2.5:2.5 (v/v/v) at RT. The reaction was brought to 37 °C by placing on a pre-heated oil bath at 37 °C and monitored by HPLC-MS. The reaction was stopped after 4h and reaction mixture placed under stream of air to remove TFA. The crude product was purified by preparative RP HPLC to afford Compound K (13 mg, 97 %, purity: 99%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC- MS elution using elution method 1; retention time: 2.89 min; MS (positive ESI): found m/z 1009.0 [M+H] ⁺ ; C48H70N11O13 (calc. 1008.5). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C48H70N11O131008.5149; Found 1008.5157. ¹ H NMR (700 MHz, DMSO-d6) į 13.14 (br s, 2H), 10.71 (br s, 1H), 9.84 (s, 1H), 8.95 (t, J = 5.9 Hz, 1H), 7.93 (br s, 1H), 7.29 – 7.24 (m, 4H), 6.58 (s, 1H), 6.57 (s, 1H), 6.36 (s, 1H), 3.92 (d, J = 12.9 Hz, 2H), 3.29 – 3.20 (m, 1H), 3.19 – 3.13 (m, 2H), 3.07 (d, J = 5.6 Hz, 6H), 2.93 – 2.87 (m, 1H), 2.61 – 2.53 (m, 4H), 2.42 – 2.33 (m, 3H), 2.00 – 1.83 (m, 2H), 1.71 – 1.64 (m, 1H), 1.56 (app. dd, J = 13.3, 3.6 Hz, 2H), 1.09 – 1.05 (m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 0.80 (d, J = 6.8 Hz, 6H). *Protons obscured by H2O and DMSO not reported. Example 12: Synthesis of 2,2',2''-(10-((R)-1-Carboxy-4-(((S)-4-carboxy-1-((2-(4-(4-(3 -(2,4- dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-tri azol-4-yl)benzyl)piperidin-1-yl)- 2-oxoethyl)amino)-1-oxobutan-2-yl)amino)-4-oxobutyl)-1,4,7,1 0-tetraazacyclododecane-1,4,7- triyl)triacetic acid (Compound L) O O ^t Bu N O N O NH•HCl O N N O ^t Bu O ^t N Bu BuO ^t N O N O O N HBTU, DIPEA, DMF HO O HO N O ^t Bu HO O N N N BuO ^t Step 1 OH N N H N O N N H OH Intermediate 1-C Intermediate 12-A O OH N O N O N N N OH TFA:TIPS:H ₂ O 95:2.5:2.5 HO 37 °C O Step 2 HO O N N N N H OH Compound L Step 1: Synthesis of tri-tert-Butyl 2,2',2''-(10-(2-(4-(4-(3-(2,4-dihydroxy-5-isopropylphenyl)-5 - (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2-oxoethyl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetate (Intermediate 12-A) To a 20 mL scintillation vial with a stir bar was added 2-(4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)- 1,4,7,10-tetraazacyclododecan-1-yl)acetic acid, DOTA-tris( ^t Bu)ester, (20.2 mg, 0.04 mmol, 1 equiv.) and DMF (2 mL). The reaction mixture was cooled to 0 °C and DIPEA, (25 μL, 18.2 mg, 0.14 mmol, 4 equiv.), followed by HBTU, (13.6 mg, 0.04 mmol, 1 equiv.) was added and stirred for 10 min at 0 °C. The solution was brought to RT and stirred for 15 min and then Intermediate 1-C (18 mg, 0.04 mmol, 1 equiv.) was added as a solid. Stirred at RT and reaction monitored by HPLC-MS. The reaction was stopped after 4 h and solvent evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 12-A (38 mg, 73%, purity: 85%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 2; retention time: 2.44 min; MS (positive ESI): found m/z 1018.0 [M+H] ⁺ ; C54H84N9O10 (calc.1018.6). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C54H84N9O10 1018.6336; Found 1018.6345. ¹ H NMR (700 MHz, DMSO-d6) į 9.88 (br s, 1H), 8.96 (t, J = 5.9 Hz, 1H), 7.34 (br s, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 6.55 (s, 1H), 6.37 (s, 1H), 4.32 (d, J = 12.8 Hz, 1H), 4.13 (br s, 5H), 3.67 – 3.62 (m, 2H), 3.16 (p, J = 6.9 Hz, 2H), 3.08 – 3.00 (m, 1H), 2.98 – 2.86 (m, 3H), 2.65 – 2.53 (m, 3H), 1.86 – 1.78 (m, 1H), 1.70 (d, J = 12.6 Hz, 1H), 1.62 (d, J = 12.6 Hz, 1H), 1.52 – 1.35 (m, 32H), 1.23 (t, J = 10.4 Hz, 1H), 1.06 (d, J = 10.4 Hz, 1H), 1.03 (t, J = 7.2 Hz, 3H), 0.78 (dd, J = 7.0, 3.2 Hz, 6H). Protons obscured by H2O and DMSO not reported. Step 2: Synthesis of 2,2',2''-(10-(2-(4-(4-(3-(2,4-Dihydroxy-5-isopropylphenyl)-5 - (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-2-oxoethyl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetic acid (Compound L) To a 20 mL scintillation vial with a stir bar was added Intermediate 12-A (25 mg, 21μmol) and 2.5 mL of deprotection cocktail TFA:TIPS:H2O - 95:2.5:2.5 (v/v/v) at RT. The reaction was brought to 37 °C by placing on a pre-heated oil bath at 37 °C and monitored by HPLC-MS. The reaction was stopped after 2h 30min and the reaction mixture was placed under stream of air to remove TFA. The crude product was purified by preparative RP HPLC to afford Compound L (11 mg, 48 %, purity: 99%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC- MS elution using elution method 1; retention time: 2.78 min; MS (positive ESI): found m/z 850.0 [M+H] ⁺ ; C42H60N9O10 (calc.850.4). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C42H60N9O10 850.4458; Found 850.4456. ¹ H NMR (700 MHz, DMSO-d6) į 12.95 (br s, 2H), 9.85 (br s, 1H), 8.96 (t, J = 5.9 Hz, 1H), 7.77 (br s, 1H), 7.31 – 7.25 (m, 4H), 6.57 (s, 1H), 6.36 (s, 1H), 4.39 – 4.01 (m, 6H), 3.59 (d, J = 13.3 Hz, 1H), 3.39 (br s, 8H), 3.19 – 3.13 (m, 2H), 3.09 (d, J = 17.5 Hz, 2H), 2.99 – 2.87 (m, 2H), 2.68 – 2.55 (m, 3H), 1.85 – 1.79 (m, 1H), 1.68 – 1.63 (m, 2H), 1.28 – 1.21 (m, 1H), 1.16 – 1.09 (m, 1H), 1.04 (t, J = 7.2 Hz, 3H), 0.81 (d, J = 6.9 Hz, 6H). *Protons obscured by H ₂ O and DMSO not reported. Example 13: Synthesis of (R)-2,2',2''-(10-(1-Carboxy-4-(4-(4-(3-(2,4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-4-oxobutyl)- 1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (Compound M) B _uO ^{t O} O BuO ^{t N} _N O N _N ^Ot Bu NH.HCl N B _uO ^{t O} O O _O ^OtBu BuO ^{t N} _N HBTU, DIPEA, DMF O _HO ^HN _{N N} ^Ot Bu Step HO O N HO 1 N O O t ^Bu N N N _O ^O OH H OH N N Intermediate 1-C Intermediate 13-A H _O ^O O HO ^N _N O N _N ^OH N O TFA:TIPS:H ₂ O 95:2.5:2.5 _O ^OH 37 °C Step 2 HO O N N N N H OH Compound M Step 1: Synthesis of tri-tert-Butyl 2,2',2''-(10-(1-(tert-butoxy)-5-(4-(4-(3-(2,4-dihydroxy-5- isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)be nzyl)piperidin-1-yl)-1,5- dioxopentan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl )(R)-triacetate (Intermediate 13- A) To a 20 mL scintillation vial with a stir bar was added (R)-DOTAGA( ^t Bu) ₄ (15 mg, 0.02 mmol, 1 equiv.), followed by THF (0.9 mL) and DMF (0.1 mL). The reaction mixture was cooled to 0 °C and DIPEA, (11.3 μL, 8.4 mg, 0.06 mmol, 3 equiv.) and HBTU, (11 mg, 0.03 mmol, 1.3 equiv.) were added and stirred for 10 min at 0 °C. The solution was brought to RT and stirred for 15 min and then Intermediate 1-C (12 mg, 0.02 mmol, 1 equiv.) was added as solution in THF (0.4 mL) and DMF (0.3 mL) along with 5 μL DIPEA. The reaction was stirred at RT and was monitored by HPLC-MS. The reaction was stopped after 2h and solvent was evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 13-A (8.6 mg, 33%, purity: 96%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC- MS elution using elution method 2; retention time: 2.64 min; MS (positive ESI): found m/z 1146.5 [M+H] ⁺ ; C61H96N9O12 (calc. 1146.7). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C61H96N9O121146.7173; Found 1146.7145. ¹ H NMR (700 MHz, DMSO-d6) į 10.67 (br s, 2H), 9.80 (br s, 1H), 8.96 (t, J = 6.5 Hz, 1H), 7.31 – 7.23 (m, 5H), 6.56 (d, J = 4.0 Hz, 1H), 6.36 (d, J = 2.3 Hz, 1H), 4.36 (s, 3H), 3.90 – 3.78 (m, 4H), 3.72 (br s, 2H), 3.18 – 3.13 (m, 3H), 3.06 (br s, 5H), 2.94 – 2.86 (m, 4H), 2.77 (br s, 3H), 2.58 – 2.54 (m, 2H), 1.96 – 1.87 (m, 2H), 1.84 – 1.73 (m, 3H), 1.68 – 1.59 (m, 3H), 1.51 – 1.37 (m, 38H), 1.03 (t, J = 7.2 Hz, 3H), 0.80 (app. dd, J = 6.9, 2.7 Hz, 6H). *Protons obscured by H ₂ O and DMSO not reported Step 2: Synthesis of (R)-2,2',2''-(10-(1-Carboxy-4-(4-(4-(3-(2,4-dihydroxy-5-isop ropylphenyl)-5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-4-oxobutyl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetic acid (Compound M) To a 20 mL scintillation vial with a stir bar was added Intermediate 13-A (7 mg, 0.01 μmol) and 0.6 mL of deprotection cocktail TFA:TIPS:H2O - 95:2.5:2.5 (v/v/v) DW^^^^^^After 5 min the reaction was brought to RT and was monitored by HPLC-MS. The reaction was stopped after 18h and reaction mixture was placed under stream of air to remove TFA. The crude product was purified by preparative RP HPLC to afford Compound M (4.3 mg, 79%, purity: 99%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 2.83 min; MS (positive ESI): found m/z 922.2 [M+H] ⁺ ; C ₄₅ H ₆₄ N ₉ O ₁₂ (calc. 922.5). HRMS (ESI-TOF) m/z: [M - H]- Calcd for C ₄₅ H ₆₂ N ₉ O ₁₂ 920.4523; Found 920.4518. ¹ H NMR (700 MHz, DMSO-d6) į 9.80 (br s, 1H), 8.96 (t, J = 5.9 Hz, 1H), 7.27 (d, J = 4.1 Hz, 4H), 6.57 (s, 1H), 6.35 (s, 1H), 4.36 (t, J = 14.6 Hz, 2H), 3.89 – 3.77 (m, 5H), 3.19 – 3.13 (m, 5H), 3.07 (s, 1H), 2.98 – 2.87 (m, 6H), 2.63 – 2.52 (m, 5H), 1.92 (s, 1H), 1.81 – 1.75 (m, 2H), 1.66 (d, J = 12.6 Hz, 1H), 1.61 (d, J = 12.6 Hz, 1H), 1.15 – 1.12 (m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 1.02 – 0.97 (m, 2H), 0.81 (d, J = 6.8 Hz, 6H). *Protons obscured by H ₂ O and DMSO not reported. Example 14: Synthesis of (R)-2,2',2''-(10-(4-(4-(4-(3-(2,4-bis(Benzyloxy)-5-isopropyl phenyl)-5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-1-carboxy-4-oxobutyl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetic acid (Compound N) _BuO ^{t O} O BuO ^{t N} _N NH•HCl O B _uO ^{t O} _N ^Ot Bu O _N N O BuO ^{t N} _N HBTU, DIPEA, DMF O O ^t Bu O N _BnO ^N _N ^Ot Bu H HO Step 1 N O O _O ^OtBu BnO O N ^N N OBn N N N H OBn Intermediate 2-B Intermediate 14-A H _O ^O O HO ^N _N O N _N ^OH N O TFA:TIPS:H ₂ O 95:2.5:2.5 O OH 37 °C Step 2 BnO O N N N N H OBn Compound N Step 1: Synthesis of tri-tert-Butyl 2,2',2''-(10-(5-(4-(4-(3-(2,4-bis(benzyloxy)-5-isopropylphen yl)- 5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1- yl)-1-(tert-butoxy)-1,5-dioxopentan- 2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)(R)-triacet ate (Intermediate 14-A) To a 20 mL scintillation vial with a stir bar was added (R)-DOTAGA( ^t Bu)4 (24.5 mg, 0.03 mmol, 1 equiv.) and 2 mL DMF. The reaction mixture cooled to 0 °C and DIPEA, (30.3 μL, 22.5 mg, 0.17 mmol, 5 equiv.), followed by HBTU, (13.5 mg, 0.03 mmol, 1 equiv.) were added and stirred for 15 min at 0 °C. The solution was brought to RT and stirred for 15 min and then Intermediate 2-B (23 mg, 0.03 mmol, 1 equiv.) was added as a solid. The reaction was stirred at rt and was monitored by HPLC-MS. The reaction was stopped after 16 h and solvent was evaporated under vacuum to give the crude product, which was purified by RP chromatography to afford Intermediate 14-A (47 mg, 83%, purity: 95%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 6.31 min; MS (positive ESI): found m/z 1327.0 [M+H] ⁺ ; C ₇₅ H ₁₀₈ N ₉ O ₁₂ (calc.1326.8). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C ₇₅ H ₁₀₈ N ₉ O ₁₂ 1326.8112; Found 1326.8142. ¹ H NMR (700 MHz, DMSO- d6) į 8.98 (td, J = 6.1, 2.6 Hz, 1H), 7.41 – 7.38 (m, 4H), 7.38 – 7.30 (m, 5H), 7.28 – 7.24 (m, 2H), 7.08 (dd, J = 15.5, 8.0 Hz, 2H), 7.04 – 6.98 (m, 3H), 6.78 (s, 1H), 5.08 (s, 2H), 4.97 (s, 2H), 4.34 – 4.30 (m, 1H), 3.91 – 3.65 (m, 3H), 3.28 (br s, 1H), 3.20 – 3.15 (m, 2H), 3.14 – 3.00 (m, 2H), 2.94 – 2.85 (m, 1H), 2.79 – 2.63 (m, 2H), 2.49 – 2.41 (m, 2H), 1.77 – 1.70 (m, 1H), 1.60 – 1.51 (m, 2H), 1.47 (br s, 11H), 1.43 – 1.34 (m, 25H), 1.05 (t, J = 7.2 Hz, 3H), 1.02 – 0.99 (m, 6H), 0.97 – 0.90 (m, 1H). *Protons obscured by H2O and DMSO not reported. Step 2: Synthesis of (R)-2,2',2''-(10-(4-(4-(4-(3-(2,4-bis(Benzyloxy)-5-isopropyl phenyl)-5- (ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)benzyl)piperidin-1-yl )-1-carboxy-4-oxobutyl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetic acid (Compound N) To a 20 mL scintillation vial with a stir bar was added Intermediate 14-A (25 mg, 18.65 μmol, 1 equiv.) and 2.5 mL of deprotection cocktail TFA:TIPS:H ₂ O - 95:2.5:2.5 (v/v/v) at RT. The reaction was brought to 37 °C by placing on a pre-heated oil bath at 37 °C and monitored by HPLC-MS. The reaction was stopped after 2h30min and the reaction mixture was placed under stream of air to remove TFA. The crude product was purified by preparative RP HPLC to afford Compound N (15 mg, 60%, purity: 99%) as a white solid as the TFA salt. An aliquot was analyzed by HPLC-MS elution using elution method 1; retention time: 4.37 min; MS (positive ESI): found m/z 1102.2 [M+H] ⁺ ; C59H76N9O12 (calc. 1102.6). HRMS (ESI-TOF) m/z: [M + H] ⁺ Calcd for C ₅₉ H ₇₆ N ₉ O ₁₂ 1102.5608; Found 1102.5624. ¹ H NMR (700 MHz, DMSO-d6) į 13.16 (br s, 2H), 8.98 (t, J = 5.9 Hz, 1H), 7.40 – 7.38 (m, 4H), 7.37 – 7.30 (m, 4H), 7.25 (dd, J = 7.0, 1.7 Hz, 2H), 7.09 (dd, J = 8.5, 2.5 Hz, 2H), 7.03 (d, J = 1.6 Hz, 1H), 6.99 (dd, J = 8.4, 2.3 Hz, 2H), 6.77 (s, 1H), 5.08 (s, 2H), 4.95 (app. d, J = 2.9 Hz, 2H), 4.41 – 4.26 (m, 1H), 3.90 – 3.85 (m, 15H), 3.79 (t, J = 15.0 Hz, 1H), 3.56 – 3.24 (m, 5H), 3.21 – 3.14 (m, 2H), 3.14 – 3.06 (m, 1H), 2.96 – 2.86 (m, 2H), 2.62 – 2.54 (m, 1H), 2.50 – 2.41 (m, 2H), 1.99 – 1.84 (m, 1H), 1.77 – 1.69 (m, 1H), 1.58 (d, J = 12.3 Hz, 1H), 1.52 – 1.49 (m, 1H), 1.11 – 1.07 (m, 1H), 1.05 (t, J = 7.2 Hz, 3H), 1.01 (d, J = 6.9 Hz, 6H), 0.98 – 0.90 (m, 1H). *Protons obscured by H2O and DMSO not reported. Example 15: Method for Radiolabeling Disclosed Compounds Prior to radiolabeling, a stock solution of each Compound was made by dissolving the appropriate quantity of Compound in sodium acetate buffer. Ethanol may be added up to 10% by volume to improve solubility of the compounds. A 1.5 mL Eppendorf tube was charged with the desired Compound followed by sodium acetate buffer to raise the total volume as desired (0.05- 0.5 mL). Next, a solution of [177Lu]LuCl3 or [111In]InCl3 or [225Ac]AcNO3 (or [225Ac]AcCl3) in hydrochloric acid solution was added and the mixture was heated. After heating the reaction for a desired amount of time, iTLC analysis of the reaction mixture (solid phase: Silica gel (SG) or silicic acid (SA) plate; mobile phase: 0.02 M citrate buffer with 5 % MeOH) indicated an acceptable radiochemical conversion (RCC), typically >95%. To the reaction mixture, sodium acetate buffer solutions of sodium L-ascorbate and diethylenetriamine-pentaacetic acid calcium trisodium salt hydrate (DTPA) were added. iTLC and reverse phase HPLC (elution method 5) at end-of-synthesis (EOS) indicated the formation of the desired radiolabeled products in typically >95% radiochemical purity (RCP). Table 1: Radiolabeling of Compounds with [177Lu]LuCl3. Compound RCP of 177Lu-Compound at EOS Compound A >99% Compound B 99% Compound C 95% Compound D >99% Compound E >99% Compound F >99% Compound G >99% Compound H >99% Compound I >99% Compound J 98% Compound K >99% Compound L >99% Compound M >99% Compound N >99% Table 2: Radiolabeling of Compounds with [111In]InCl ₃ . Compound RCP of 111In-Compound at EOS Compound A >99% Compound B 97% Compound C 90% Compound D >99% Compound G >99% Compound M >99% Table 3: Radiolabeling of Compounds with [225Ac]. Compound RCP of 225Ac-Compound at EOS Compound A 98% Compound D >99% Compound G >99% Below shows the sample radiolabeling of a Compound featuring a DOTAGA chelator with [177Lu]LuCl ₃ , [111In]InCl ₃ , or [225Ac] . O ^O _OH H O O N O N N O O H N N O OH HO N N M ³⁺ O HO Compound D O Sodium acetate buffer HO HN N O OH N N

^O O _O H O O N O N N O O H N N O O M O N N Na O O O HO HN N O N N M = 225Ac : 225Ac-Compound D OH _{M = 111In :} ^{111In-Compound D} M = 177Lu : 177Lu-Compound D Below shows the sample radiolabeling of a Compound featuring a DOTA chelator with [177Lu]LuCl ₃ , [111In]InCl ₃ , or [225Ac] . O O OH O N N O _N O ^O M _N O N N N N HO M ³⁺ N N O HO O Sodium acetate buffer O O HO HN HO HN N N O O OH N N OH N N M = 225Ac : 225Ac-Compound L Compound L M = 111In : 111In-Compound L M = 177Lu : 177Lu-Compound L Example 16: In Vitro HSP90 Binding Studies of Radiopharmaceuticals Comprising Compounds of Formula I HSP90 binding was determined using a cell-free binding affinity assay, where recombinant HSP90 protein was coated onto a Reacti-Bind® microtiter plate. Plates were incubated at 4 °C overnight and then washed 3 times with cold PBS containing 0.05% Tween-20 (PBS-T). Plates were equilibrated to room temperature, blocked for 1 hour on ice with PBS-T containing 0.2% gelatin, followed by 3 washes with PBS-T. Radiolabeled (Lu-177) conjugates with increasing concentrations were incubated in the absence or presence of unlabeled conjugate, and incubated at 37 °C for 1 hour with gentle shaking. Wells were then rinsed three times with PBS-T and stripped with a solution of 20 mM sodium acetate, pH 3.0 for up to 20 minutes at room temperature, followed by neutralization with an equal amount of 0.1N NaOH solution. Samples were transferred into gamma counting tubes and analyzed for Lu-177 content by gamma counter. Results were plotted relative to molar concentration of labeled conjugate, where specific binding affinity (K _d ) is calculated using Graph Pad Prism. Binding affinity (K _d ) results are summarized in Table 4^^ZKHUH^^^Q0^^^$^^^5 nM, ^^Q0^^^%^^^^^^^Q0^^DQG^C > 100 nM. Table 4: Binding affinities (K _d ^^RI^VHOHFWHG^FRPSRXQGV^WR^UHFRPELQDQW^+VS^^Į^RU^ȕ^ isoforms. C ^{ompound Kd (nM)} + _{VS^^Į +VS^^ȕ Compound A} ^{A A} C _{ompound B} ^A _{A Compound C} ^A _{A Compound D A} ^A C _{ompound E A} ^A C _{ompound F} ^{A A} Compound G A A Compound H A A C _{ompound I A} ^B Compound J A A C _{ompound K} ^{A A} Compound L A A C _{ompound M A} ^A C _{ompound N} ^{C C} Example 17: Biodistribution Studies of Radiopharmaceuticals Comprising Compounds of Formula I In an animal model, Lutetium-177 (Lu-177) or Indium (In-111) accumulation was measured in tumor, blood and healthy tissues of subcutaneous xenograft tumor-bearing mice. Tumor bearing mice were GRVHG^ZLWK^^^^^&L^RI^HLWKHU^/X-177 or In-111 conjugates. At the time points indicated (1h, 4h, 24h), mice were sacrificed, and tumor, liver, kidneys and blood were isolated. All tissues were analyzed for Lu-177 or In-111 content by gamma counter, and radioligand uptake was determined as percentage injected dose per gram of tissue (%ID/g). Average radioligand uptake (%ID/g, n = 3) is summarized in Table 5. Table 5. Biodistribution of selected compounds in tumor-bearing mice. Compound BioD (%ID/g) Lu-177 or In- 1h 4h 24h 111 ^tumor _{blood liver kidney} ^tumor _{blood liver kidney} ^tumor _{blood liver kidney} ^{Compound A 14.60 13.93} _{5.01 6.47} ^{20.85 6.70} _{6.44 8.47} ^{14.98 0.52} _{2.81 5.55} Compound B 12.97 15.33 7.38 7.28 10.41 7.80 7.25 6.34 5.59 0.37 1.38 0.87 Compound C 7.37 17.08 4.50 7.50 11.51 11.95 5.48 7.83 5.74 0.84 2.19 2.31 Compound D 9.22 16.35 7.43 9.41 13.01 9.40 7.69 10.91 10.19 0.48 3.43 6.06 Compound G 6.74 10.45 17.19 8.00 5.71 5.25 18.43 7.56 6.37 0.25 5.82 5.68 Compound I 16.19 10.09 10.47 8.31 16.46 3.40 10.08 8.87 10.15 0.20 3.16 6.05 Compound L 4.82 7.68 32.84 5.35 5.42 0.73 39.74 3.65 3.25 0.18 10.38 2.57 Example 18: In Vivo Studies of Radiopharmaceuticals Comprising Compounds of Formula I Using an in vivo model, overall survival and tumor growth regression in HSP90 expressing xenograft tumor-bearing mice was evaluated to determine the in vivo efficacy of the compounds of Formula I. Mice implanted with HSP90 expressing xenograft tumors were treated with various concentrations and doses of the compounds of Formula I to evaluate in vivo efficacy. To determine the most effective dose range, preclinical dose escalation studies were conducted. Average tumor growth suppression (n = 5 animals/group) in response to a dose escalation of 225Ac-Compound D in comparison to vehicle (buffer control) and non-radiolabeled Compound D is presented in Figure 1. It was observed that 225Ac-Compound D administered at 3 μCi was efficacious in significantly suppressing the tumor growth. OTHER EMBODIMENTS [158] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described herein. Such equivalents are intended to be encompassed by the following claims.