Title:
TETRAAZA- OR N2S2- COMPLEXANTS, AND THEIR USE IN RADIODIAGNOSTICS OR RADIOTHERAPY
Document Type and Number:
WIPO Patent Application WO1998043678
Kind Code:
A3
Abstract:
The present invention provides for substituted metal chelating compounds of the formula:
in which at least two of the chelating atoms are nitrogen which are directly attached to aromatic rings and one or more of those nitrogen atoms has attached thereto a substituent other than hydrogen, and methods for making and using these compounds. Another aspect of the invention provides for the use of the chelation compounds described above in methods for diagnostic and therapeutic purposes. A diagnostic method is described for detecting the presence or absence of a target site within a mammalian host. This method comprises providing to cells a diagnostically effective dose of a compound of the present invention which contains a metal radionuclide, such as 99m Tc and/or 111 In, and detecting the biodistribution of the radionuclide. A therapeutic method is described for delivering a radionuclide, such as 186 Re/ 188 Re, 90 Y, and 153 Sm, to a target site within a mammalian host. This method comprises providing to cells a therapeutically effective dose of a chelate compound of the present invention.
Inventors:
KASINA SUDHAKAR
Application Number:
PCT/US1998/005858
Publication Date:
March 04, 1999
Filing Date:
March 26, 1998
Export Citation:
Assignee:
NEORX CORP (US)
International Classes:
A61K51/00; A61K51/04; A61K51/08; A61P35/00; C07C229/16; C07C229/18; C07C323/34; C07D257/10; C07D265/32; C07D285/00; C07D333/36; C07D495/04; C07D495/14; C07F5/00; C07F9/22; C07F9/38; C07F9/6524; C07F9/6553; C07F9/6561; C07F13/00; (IPC1-7): A61K49/00
Domestic Patent References:
| WO1995032192A1 | 1995-11-30 | |||
| WO1997001360A2 | 1997-01-16 | |||
| WO1994026754A1 | 1994-11-24 | |||
| WO1998004294A2 | 1998-02-05 |
Foreign References:
| EP0603403A1 | 1994-06-29 | |||
| US5021571A | 1991-06-04 | |||
| US5362475A | 1994-11-08 | |||
| US5334729A | 1994-08-02 | |||
| US5676928A | 1997-10-14 |
Other References:
TSIEN R Y: "New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures", BIOCHEMISTRY 1980, VOL. 19, NO. 11, PAGE(S) 2396-2404, XP002074821
"Rhenium-186, Samarium-153, Technetium-99m, Yttrium-90", REYNOLDS J E F (ED ): MARTINDALE - THE EXTRA PHARMACOPOEIA, ED. 31, 1996, Royal Pharmaceutical Society, London, GB, pages 1467 - 1468, XP002074822
"Indium-111", REYNOLDS J E F (ED ): MARTINDALE - THE EXTRA PHARMACOPOEIA, ED. 31, 1996, Royal Pharmaceutical Society, London, GB, pages 1465, XP002074823
S. BUDAVARI ET AL.: "THE MERCK INDEX, AN ENCYCLOPEDIA OF CHEMICALS, DRUGS, AND BIOLOGICALS", 1996, MERCK & CO, INC, WHITEHOUSE STATION, US, XP002074824
STRATTON J R ET AL: "SELECTIVE UPTAKE OF RADIOLABELED ANNEXIN V ON ACUTE PORCINE LEFT ATRIAL THROMBI", CIRCULATION, vol. 92, no. 10, 15 November 1995 (1995-11-15), pages 3113 - 3121, XP002058828
RENN O ET AL: "New approaches to delivering metal-labeled antibodies to tumors: Synthesis and characterization of new biotinyl chelate conjugates for pre-targeted diagnosis and therapy", JOURNAL OF CONTROLLED RELEASE, vol. 39, no. 2, May 1996 (1996-05-01), pages 239-249, XP004037330
LOUW W K A ET AL: "Evaluation of Samarium-153 and Holmium-166-EDTMP in the Normal Baboon Model", NUCLEAR MEDICINE AND BIOLOGY, vol. 23, no. 8, November 1996 (1996-11-01), pages 935-940, XP004073001
WU C ET AL: "INVESTIGATIONS OF N-LINKED MACROCYCLES FOR 111IN AND 90Y LABELING OF PROTEINS", INTERNATIONAL JOURNAL OF RADIATION APPLICATIONS AND INSTRUMENTATION PART B: NUCLEAR MEDICINE AND BIOLOGY, vol. 19, no. 2, 1992, pages 239 - 244, XP002064857
LEVER S Z ET AL: "PULMONARY ACCUMULATION OF NEUTRAL DIAMINE DITHIOL COMPLEXES OF TECHNETIUM-99M", JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 83, no. 6, 1 June 1994 (1994-06-01), pages 802 - 809, XP000446373
TADASHI FUJISAWA ET AL: "CRITICAL CURRENT DENSITIES IN SUPERCONDUCTING Y-BA-CU-O PREPARED BY CHELATING METHOD", JAPANESE JOURNAL OF APPLIED PHYSICS, vol. 29, no. 10, 1 October 1990 (1990-10-01), pages 1914 - 1917, XP000223980
SUBRAMANIAN K M ET AL: "A NEW RADIOCHEMICAL METHOD TO DETERMINE THE STABILITY CONSTANTS OF METAL CHELATES ATTACHED TO A PROTEIN", JOURNAL OF NUCLEAR MEDICINE, vol. 31, no. 4, 1 April 1990 (1990-04-01), pages 480 - 488, XP000128746
SUN Y: "TARGETING RADIOPHARMACEUTICALS-II. EVALUATION OF NEW TRIVALENT METAL COMPLEXES WITH DIFFERENT OVERALL CHARGES", INTERNATIONAL JOURNAL OF RADIATION APPLICATIONS AND INSTRUMENTATION PART B: NUCLEAR MEDICINE AND BIOLOGY, vol. 18, no. 3, 1 January 1991 (1991-01-01), pages 323 - 330, XP000215616
PAPADOPOULOS M ET AL: "99MTC-DADT COMPLEXES SUBSTITUTED WITH HETEROCYCLIC AMINES: EFFECT OF SUBSTITUTION ON IN VIVO REACTIVITY", NUCLEAR MEDICINE AND BIOLOGY, vol. 20, no. 1, 1 January 1993 (1993-01-01), pages 105 - 115, XP000336597
SUBRAMANIAN G ET AL: "Indium-113m-labeled polyfunctional phosphonates as bone-imaging agents.", J NUCL MED, NOV 1975, VOL. 16, NO. 11, PAGE(S) 1080-4, XP002084585
SCHOMACKER K ET AL: "Influence on extratumoral organ activities of tumor-affinity samarium-153 preparations]", NUKLEARMEDIZIN, MAR 1997, VOL. 36, NO. 2, PAGE(S) 47-51, XP002084586
SCHOMACKER K ET AL: "[The effect of ethylenediaminetetramethylenephosphonate on the biodistribution of tumor-seeking radionuclides]", NUKLEARMEDIZIN, FEB 1993, VOL. 32, NO. 1, PAGE(S) 23-6, XP002084587
DEWANJEE M.K.: "Localization of 113m-In- and 67-Ga-labeled poly- methylene- phosphonates in myocardial infarct", NUKL. MED., 1977, VOL. 16, NO. 4, PAGE(S) 151-156, XP002084588
VOLKERT W A ET AL: "SKELETAL UPTAKE PROPERTIES OF TECHNETIUM-99M-LABELED MULTIDENTATE PHOSPHONATE LIGANDS", J LABELLED COMPD RADIOPHARM, 1984, VOL. 21, NO. 11-12, PAGE(S) 1063-1065, XP002084589
VOLKERT W.A. ET AL: "In vivo skeletal localization properties of 99m-Tc complexes of large phosphonate ligands", NUCL. MED. BIOL., 1986, VOL. 13, NO. 1, PAGE(S) 31-37, XP002084590
GOECKELER W.F. ET AL: "Skeletal localization of samarium-153 chelates: Potential therapeutic bone agents", J. NUCL. MED., 1987, VOL. 28, NO. 4, PAGE(S) 495-504, XP002084591
STAHL W ET AL: "99m Technetium labelling of antibodies using methylphosphonylated, bifunctional cyclams as chelators", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, VOL. 4, NO. 21, PAGE(S) 2597-2600., XP002084592
KASINA S ET AL: "Preformed chelate Tc-99m radiolabeling of r-annexin V for arterial thrombus imaging", JOURNAL OF NUCLEAR MEDICINE, 1996, VOL. 37, NO. 5 SUPPL., PAGE(S) 29P., XP002084593
BLANKENBERG F G ET AL: "Increased localization of Tc-99m hydrazino nicotinamide (HYNIC) labeled annexin V lipocortin in lymphatic tissue of animals treated with dexamethasone", JOURNAL OF NUCLEAR MEDICINE, 1997, VOL. 38, NO. 5 SUPPL., PAGE(S) 268P-269P., XP002084594
"Rhenium-186, Samarium-153, Technetium-99m, Yttrium-90", REYNOLDS J E F (ED ): MARTINDALE - THE EXTRA PHARMACOPOEIA, ED. 31, 1996, Royal Pharmaceutical Society, London, GB, pages 1467 - 1468, XP002074822
"Indium-111", REYNOLDS J E F (ED ): MARTINDALE - THE EXTRA PHARMACOPOEIA, ED. 31, 1996, Royal Pharmaceutical Society, London, GB, pages 1465, XP002074823
S. BUDAVARI ET AL.: "THE MERCK INDEX, AN ENCYCLOPEDIA OF CHEMICALS, DRUGS, AND BIOLOGICALS", 1996, MERCK & CO, INC, WHITEHOUSE STATION, US, XP002074824
STRATTON J R ET AL: "SELECTIVE UPTAKE OF RADIOLABELED ANNEXIN V ON ACUTE PORCINE LEFT ATRIAL THROMBI", CIRCULATION, vol. 92, no. 10, 15 November 1995 (1995-11-15), pages 3113 - 3121, XP002058828
RENN O ET AL: "New approaches to delivering metal-labeled antibodies to tumors: Synthesis and characterization of new biotinyl chelate conjugates for pre-targeted diagnosis and therapy", JOURNAL OF CONTROLLED RELEASE, vol. 39, no. 2, May 1996 (1996-05-01), pages 239-249, XP004037330
LOUW W K A ET AL: "Evaluation of Samarium-153 and Holmium-166-EDTMP in the Normal Baboon Model", NUCLEAR MEDICINE AND BIOLOGY, vol. 23, no. 8, November 1996 (1996-11-01), pages 935-940, XP004073001
WU C ET AL: "INVESTIGATIONS OF N-LINKED MACROCYCLES FOR 111IN AND 90Y LABELING OF PROTEINS", INTERNATIONAL JOURNAL OF RADIATION APPLICATIONS AND INSTRUMENTATION PART B: NUCLEAR MEDICINE AND BIOLOGY, vol. 19, no. 2, 1992, pages 239 - 244, XP002064857
LEVER S Z ET AL: "PULMONARY ACCUMULATION OF NEUTRAL DIAMINE DITHIOL COMPLEXES OF TECHNETIUM-99M", JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 83, no. 6, 1 June 1994 (1994-06-01), pages 802 - 809, XP000446373
TADASHI FUJISAWA ET AL: "CRITICAL CURRENT DENSITIES IN SUPERCONDUCTING Y-BA-CU-O PREPARED BY CHELATING METHOD", JAPANESE JOURNAL OF APPLIED PHYSICS, vol. 29, no. 10, 1 October 1990 (1990-10-01), pages 1914 - 1917, XP000223980
SUBRAMANIAN K M ET AL: "A NEW RADIOCHEMICAL METHOD TO DETERMINE THE STABILITY CONSTANTS OF METAL CHELATES ATTACHED TO A PROTEIN", JOURNAL OF NUCLEAR MEDICINE, vol. 31, no. 4, 1 April 1990 (1990-04-01), pages 480 - 488, XP000128746
SUN Y: "TARGETING RADIOPHARMACEUTICALS-II. EVALUATION OF NEW TRIVALENT METAL COMPLEXES WITH DIFFERENT OVERALL CHARGES", INTERNATIONAL JOURNAL OF RADIATION APPLICATIONS AND INSTRUMENTATION PART B: NUCLEAR MEDICINE AND BIOLOGY, vol. 18, no. 3, 1 January 1991 (1991-01-01), pages 323 - 330, XP000215616
PAPADOPOULOS M ET AL: "99MTC-DADT COMPLEXES SUBSTITUTED WITH HETEROCYCLIC AMINES: EFFECT OF SUBSTITUTION ON IN VIVO REACTIVITY", NUCLEAR MEDICINE AND BIOLOGY, vol. 20, no. 1, 1 January 1993 (1993-01-01), pages 105 - 115, XP000336597
SUBRAMANIAN G ET AL: "Indium-113m-labeled polyfunctional phosphonates as bone-imaging agents.", J NUCL MED, NOV 1975, VOL. 16, NO. 11, PAGE(S) 1080-4, XP002084585
SCHOMACKER K ET AL: "Influence on extratumoral organ activities of tumor-affinity samarium-153 preparations]", NUKLEARMEDIZIN, MAR 1997, VOL. 36, NO. 2, PAGE(S) 47-51, XP002084586
SCHOMACKER K ET AL: "[The effect of ethylenediaminetetramethylenephosphonate on the biodistribution of tumor-seeking radionuclides]", NUKLEARMEDIZIN, FEB 1993, VOL. 32, NO. 1, PAGE(S) 23-6, XP002084587
DEWANJEE M.K.: "Localization of 113m-In- and 67-Ga-labeled poly- methylene- phosphonates in myocardial infarct", NUKL. MED., 1977, VOL. 16, NO. 4, PAGE(S) 151-156, XP002084588
VOLKERT W A ET AL: "SKELETAL UPTAKE PROPERTIES OF TECHNETIUM-99M-LABELED MULTIDENTATE PHOSPHONATE LIGANDS", J LABELLED COMPD RADIOPHARM, 1984, VOL. 21, NO. 11-12, PAGE(S) 1063-1065, XP002084589
VOLKERT W.A. ET AL: "In vivo skeletal localization properties of 99m-Tc complexes of large phosphonate ligands", NUCL. MED. BIOL., 1986, VOL. 13, NO. 1, PAGE(S) 31-37, XP002084590
GOECKELER W.F. ET AL: "Skeletal localization of samarium-153 chelates: Potential therapeutic bone agents", J. NUCL. MED., 1987, VOL. 28, NO. 4, PAGE(S) 495-504, XP002084591
STAHL W ET AL: "99m Technetium labelling of antibodies using methylphosphonylated, bifunctional cyclams as chelators", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, VOL. 4, NO. 21, PAGE(S) 2597-2600., XP002084592
KASINA S ET AL: "Preformed chelate Tc-99m radiolabeling of r-annexin V for arterial thrombus imaging", JOURNAL OF NUCLEAR MEDICINE, 1996, VOL. 37, NO. 5 SUPPL., PAGE(S) 29P., XP002084593
BLANKENBERG F G ET AL: "Increased localization of Tc-99m hydrazino nicotinamide (HYNIC) labeled annexin V lipocortin in lymphatic tissue of animals treated with dexamethasone", JOURNAL OF NUCLEAR MEDICINE, 1997, VOL. 38, NO. 5 SUPPL., PAGE(S) 268P-269P., XP002084594
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