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Last Updated: October 16, 2019

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Claims for Patent: 6,537,520

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Summary for Patent: 6,537,520
Title: Pharmaceuticals for the imaging of angiogenic disorders
Abstract:The present invention describes novel compounds of the formula: useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.
Inventor(s): Rajopadhye; Milind (Westford, MA), Edwards; D. Scott (Burlington, MA), Barrett; John A. (Groton, MA), Carpenter, Jr.; Alan P. (Carlisle, MA), Harris; Thomas D. (Samel, NH), Heminway; Stuart J. (Lowell, MA), Liu; Shuang (Chelmsford, MA), Singh; Prahlad R. (Arlington, MA)
Assignee: Bristol-Myers Squibb Pharma Company (Princeton, NJ)
Application Number:09/599,295
Patent Claims:1. A kit for treating cancer, comprising a compound, comprising: a) a targeting moiety; b) a chelator; and c) 0-1 linking groups between the targeting moiety and chelator; wherein the targeting moiety is a peptide or peptidomimetic, and binds to a .alpha..sub.v.beta..sub.3 receptor that is upregulated during angiogenesis, or a pharmaceutically acceptable salt thereof, and at least one agent selected from the group consisting of a chemotherapeutic agent and a radiosensitizer agent, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

2. A kit according to claim 1 wherein said kit comprises a plurality of separate containers, wherein at least one of said containers contains said compound, or a pharmaceutically acceptable salt thereof, and at least another of said containers contains one or more agents selected from the group consisting of a chemotherapeutic agent and a radiosensitizer agent, or a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable carrier.

3. A kit according to claim 1, wherein the chemotherapeutic agent is selected from the group consisting of mitomycin, tretinoin, ribomustin, gemcitabine, vincristine, etoposide, cladribine, mitobronitol, methotrexate, doxorubicin, carboquone, pentostatin, nitracrine, zinostatin, cetrorelix, letrozole, raltitrexed, daunorubicin, fadrozole, fotemustine, thymalfasin, sobuzoxane, nedaplatin, cytarabine, bicalutamide, vinorelbine, vesnarinone, aminoglutethimide, amsacrine, proglumide, elliptinium acetate, ketanserin, doxifluridine, etretinate, isotretinoin, streptozocin, nimustine, vindesine, flutamide, drogenil, butocin, carmofur, razoxane, sizofilan, carboplatin, mitolactol, tegafur, ifosfamide, prednimustine, picibanil, levamisole, teniposide, improsulfan, enocitabine, lisuride, oxymetholone, tamoxifen, progesterone, mepitiostane, epitiostanol, formestane, interferon-alpha, interferon-2 alpha, interferon-beta, interferon-gamma, colony stimulating factor-1, colony stimulating factor-2, denileukin diftitox, interleukin-2, and leutinizing hormone releasing factor.

4. A kit according to claim 1, wherein the chemotherapeutic agent is selected from the group consisting of mitomycin, tretinoin, ribomustin, gemcitabine, vincristine, etoposide, cladribine, mitobronitol, methotrexate, doxorubicin, carboquone, pentostatin, nitracrine, zinostatin, cetrorelix, letrozole, raltitrexed, daunorubicin, fadrozole, fotemustine, thymalfasin, sobuzoxane, nedaplatin, cytarabine, bicalutamide, vinorelbine, vesnarinone, aminoglutethimide, amsacrine, proglumide, elliptinium acetate, ketanserin, doxifluridine, etretinate, isotretinoin, streptozocin, nimustine, vindesine, flutamide, drogenil, butocin, carmofur, razoxane, sizofilan, carboplatin, mitolactol, tegafur, ifosfamide, prednimustine, picibanil, levamisole, teniposide, improsulfan, enocitabine, and lisuride.

5. A kit according to claim 1, wherein the chemotherapeutic agent is selected from the group consisting of oxymetholone, tamoxifen, progesterone, mepitiostane, epitiostanol, and formestane.

6. A kit according to claim 1 wherein the chemotherapeutic agent is selected from the group consisting of interferon-alpha, interferon-2 alpha, interferon-beta, interferon-gamma, colony stimulating factor-1, colony stimulating factor-2, denileukin diftitox, interleukin-2, and leutinizing hormone releasing factor.

7. A kit according to claim 1, wherein radiosensitizer agent is selected from the group consiting of 2-(3-nitro-1,2,4-triazol-1-yl)-N-(2-methoxyethyl)acetamide, N-(3-nitro-4-quinolinyl)-4-morpholinecarboxamidine, 3-amino-1,2,4-benzotriazine-1,4-dioxide, N-(2-hydroxyethyl)-2-nitroimidazole-1-acetamide, 1-(2-nitroimidazol-1-yl)-3-(1-piperidinyl)-2-propanol, and 1-(2-nitro-1-imidazolyl)-3-(1-aziridino)-2-propanol.

8. A therapeutic radiopharmaceutical composition comprising: a metal, and a compound wherein the compound comprises: a) a chelator capable of chelating the metal; b) a targeting moiety; and c) 0-1 linking groups between the targeting moiety and chelator; wherein the targeting moiety is a peptide or peptidomimetic, and binds to .alpha..sub.v.beta..sub.3 receptor that is upregulated during angiogenesis, and wherein the composition further comprising at least one agent selected from the group consisting of a chemotherapeutic agent and a radiosensitizer agent,

or a pharmaceutically acceptable salt thereof.

9. A therapeutic radiopharmaceutical composition according to claim 8, wherein the chemotherapeutic agent is selected from the group consisting of mitomycin, tretinoin, ribomustin, gemcitabine, vincristine, etoposide, cladribine, mitobronitol, methotrexate, doxorubicin, carboquone, pentostatin, nitracrine, zinostatin, cetrorelix, letrozole, raltitrexed, daunorubicin, fadrozole, fotemustine, thymalfasin, sobuzoxane, nedaplatin, cytarabine, bicalutamide, vinorelbine, vesnarinone, aminoglutethimide, amsacrine, proglumide, elliptinium acetate, ketanserin, doxifluridine, etretinate, isotretinoin, streptozocin, nimustine, vindesine, flutamide, drogenil, butocin, carmofur, razoxane, sizofilan, carboplatin, mitolactol, tegafur, ifosfamide, prednimustine, picibanil, levamisole, teniposide, improsulfan, enocitabine, lisuride, oxymetholone, tamoxifen, progesterone, mepitiostane, epitiostanol, formestane, interferon-alpha, interferon-2 alpha, interferon-beta, interferon-gamma, colony stimulating factor-1, colony stimulating factor-2, denileukin diftitox, interleukin-2, and leutinizing hormone releasing factor.

10. A therapeutic radiopharmaceutical composition according to claim 8, wherein radiosensitizer agent is selected from the group consisting of 2-(3-nitro-1,2,4-triazol-1-yl)-N-(2-methoxyethyl)acetamide, N-(3-nitro-4-quinolinyl)-4-morpholinecarboxamidine, 3-amino-1,2,4-benzotriazine-1,4-dioxide, N-(2-hydroxyethyl)-2-nitroimidazole-1-acetamide, 1-(2-nitroimidazol-1-yl)-3-(1-piperidinyl)-2-propanol, and 1-(2-nitro-1-imidazolyl)-3-(1-aziridino)-2-propanol.

11. A method of treating cancer in a patient comprising: administering to a patient in need thereof a therapeutic radiopharmaceutical or a pharmaceutically acceptable salt thereof, and at least one agent selected from the group consisting of a chemotherapeutic agent and a radiosensitizer agent, or a pharmaceutically acceptable salt thereof, wherein the therapeutic radiopharmaceutical comprises a metal and a compound, wherein the compound comprises: a) a chelator capable of chelating the metal; b) a targeting moiety; and c) 0-1 linking groups between the targeting moiety and chelator; wherein the targeting moiety is a peptide or peptidomimetic, and binds to a .alpha..sub.v.beta..sub.3 receptor that is upregulated during angiogenesis; and wherein the metal is a radioisotope selected from the group: .sup.33 P, .sup.125 I, .sup.186 Re, .sup.188 Re, .sup.153 Sm, .sup.166 Ho, .sup.177 Lu, 149pm, .sup.90 Y, .sup.212 Bi, .sup.103 Pd, .sup.109 Pd, .sup.159 Gd, .sup.140 La, .sup.198 Au, .sup.199 Au, .sup.169 Yb, .sup.175 Yb, .sup.165 Dy, .sup.166 Dy, .sup.67 Cu, .sup.105 Rh, .sup.111 Ag, and .sup.192 Ir.

12. A method of treating cancer according to claim 11, wherein the administration is by injection or infusion.

13. A method according to claim 11 wherein administering the therapeutic radiopharmaceutical and agent is concurrent.

14. A method according to claim 11 wherein administering the therapeutic radiopharmaceutical and agent is sequential.

15. A method according to claim 11 wherein the cancer is selected from the group consisting of carcinomas of the lung, breast, ovary, stomach, pancreas, larynx, esophagus, testes, liver, parotid, biliary tract, colon, rectum, cervix, uterus, endometrium, kidney, bladder, prostate, thyroid, squamous cell carcinomas, adenocarcinomas, small cell carcinomas, melanomas, gliomas, and neuroblastomas.

16. A method according to claim 11 wherein the chemotherapeutic agent is selected from the group consisting of mitomycin, tretinoin, ribomustin, gemcitabine, vincristine, etoposide, cladribine, mitobronitol, methotrexate, doxorubicin, carboquone, pentostatin, nitracrine, zinostatin, cetrorelix, letrozole, raltitrexed, daunorubicin, fadrozole, fotemustine, thymalfasin, sobuzoxane, nedaplatin, cytarabine, bicalutamide, vinorelbine, vesnarinone, aminoglutethimide, amsacrine, proglumide, elliptinium acetate, ketanserin, doxifluridine, etretinate, isotretinoin, streptozocin, nimustine, vindesine, flutamide, drogenil, butocin, carmofur, razoxane, sizofilan, carboplatin, mitolactol, tegafur, ifosfamide, prednimustine, picibanil, levamisole, teniposide, improsulfan, enocitabine, lisuride, oxymetholone, tamoxifen, progesterone, mepitiostane, epitiostanol, formestane, interferon-alpha, interferon-2 alpha, interferon-beta, interferon-gamma, colony stimulating factor-1, colony stimulating factor-2, denileukin diftitox, interleukin-2, and leutinizing hormone releasing factor.

17. A method according to claim 11 wherein the radiosensitizer agent is selected from the group consiting of 2-(3-nitro-1,2,4-triazol-1-yl)-N-(2-methoxyethyl)acetamide, N-(3-nitro-4-quinolinyl)-4-morpholinecarboxamidine, 3-amino-1,2,4-benzotriazine-1,4-dioxide, N-(2-hydroxyethyl)-2-nitroimidazole-1-acetamide, 1-(2-nitroimidazol-1-yl)-3-(1-piperidinyl)-2-propanol, and 1-(2-nitro-1-imidazolyl)-3-(1-aziridino)-2-propanol.

18. A kit according to claim 1, wherein the linking group is present between the targeting moiety and chelator.

19. A kit according to claim 18, wherein compound is of the formula:

wherein, Q is a peptide independently selected from the group: ##STR76## K is an L-amino acid independently selected at each occurrence from the group: arginine, citrulline, N-methylarginine, lysine, homolysine, 2-aminoethylcysteine, .delta.-N-2-imidazolinylornithine, .delta.-N-benzylcarbamoylornithine, and .beta.-2-benzimidazolylacetyl-1,2-diaminopropionic acid; K is a D-amino acid independently selected at each occurrence from the group: arginine, citrulline, N-methylarginine, lysine, homolysine, 2-aminoethylcysteine, .delta.-N-2-imidazolinylornithine, .delta.-N-benzylcarbamoylornithine, and .beta.-2-benzimidazolylacetyl-1,2-diaminopropionic acid; L is independently selected at each occurrence from the group: glycine, L-alanine, and D-alanine; M is L-aspartic acid; M' is D-aspartic acid; R.sup.1 is an amino acid substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, L-valine, D-valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, 2-aminohexanoic acid, tyrosine, phenylalanine, thienylalanine, phenylglycine, cyclohexylalanine, homophenylalanine, 1-naphthylalanine, lysine, serine, ornithine, 1,2-diaminobutyric acid, 1,2-diaminopropionic acid, cysteine, penicillamine, and methionine; R.sup.2 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, 2-aminohexanoic acid, tyrosine, L-phenylalanine, D-phenylalanine, thienylalanine, phenylglycine, biphenylglycine, cyclohexylalanine, homophenylalanine, L-1-naphthylalanine, D-1-naphthylalanine, lysine, serine, ornithine, 1,2-diaminobutyric acid, 1,2-diaminopropionic acid, cysteine, penicillamine, methionine, and 2-aminothiazole-4-acetic acid; R.sup.3 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-2-aminohexanoic acid, D-tyrosine, D-phenylalanine, D-thienylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-1-naphthylalanine, D-lysine, D-serine, D-ornithine, D-1,2-diaminobutyric acid, D-1,2-diaminopropionic acid, D-cysteine, D-penicillamine, and D-methionine; R.sup.4 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-2-aminohexanoic acid, D-tyrosine, D-phenylalanine, D-thienylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-1-naphthylalanine, D-lysine, D-serine, D-ornithine, D-1,2-diaminobutyric acid, D-1,2-diaminopropionic acid, D-cysteine, D-penicillamine, D-methionine, and 2-aminothiazole-4-acetic acid; R.sup.5 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, L-valine, L-alanine, L-leucine, L-isoleucine, L-norleucine, L-2-aminobutyric acid, L-2-aminohexanoic acid, L-tyrosine, L-phenylalanine, L-thienylalanine, L-phenylglycine, L-cyclohexylalanine, L-homophenylalanine, L-1-naphthylalanine, L-lysine, L-serine, L-ornithine, L-1,2-diaminobutyric acid, L-1,2-diaminopropionic acid, L-cysteine, L-penicillamine, L-methionine, and 2-aminothiazole-4-acetic acid; provided that one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 in each Q is substituted with a bond to L.sub.n, further provided that when R.sup.2 is 2-aminothiazole-4-acetic acid, K is N-methylarginine, further provided that when R.sup.4 is 2-aminothiazole-4-acetic acid, K and K' are N-methylarginine, and still further provided that when R.sup.5 is 2-aminothiazole-4-acetic acid, K' is N-methylarginine; d is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; L.sub.n is a linking group having the formula:

and a pharmaceutically acceptable salt thereof.

20. A kit according to claim 19, wherein L is glycine; R.sup.1 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: L-valine, D-valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, tyrosine, phenylalanine, phenylglycine, cyclohexylalanine, homophenylalanine, lysine, ornithine, 1,2-diaminobutyric acid, and 1,2-diaminopropionic acid; R.sup.2 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, tyrosine, L-phenylalanine, D-phenylalanine, thienylalanine, phenylglycine, biphenylglycine, cyclohexylalanine, homophenylalanine, L-1-naphthylalanine, D-1-naphthylalanine, lysine, ornithine, 1,2-diaminobutyric acid, 1,2-diaminopropionic acid, and 2-aminothiazole-4-acetic acid; R.sup.3 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-tyrosine, D-phenylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-lysine, D-serine, D-ornithine, D-1,2-diaminobutyric acid, and D-1,2-diaminopropionic acid; R.sup.4 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-tyrosine, D-phenylalanine, D-thienylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-1-naphthylalanine, D-lysine, D-ornithine, D-1,2-diaminobutyric acid, D-1,2-diaminopropionic acid, and 2-aminothiazole-4-acetic acid; R.sup.5 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: L-valine, L-alanine, L-leucine, L-isoleucine, L-norleucine, L-2-aminobutyric acid, L-tyrosine, L-phenylalanine, L-thienylalanine, L-phenylglycine, L-cyclohexylalanine, L-homophenylalanine, L-1-naphthylalanine, L-lysine, L-ornithine, L-1,2-diaminobutyric acid, L-1,2-diaminopropionic acid, and 2-aminothiazole-4-acetic acid; d is selected from 1, 2, and 3; W is independently selected at each occurrence from the group: O, NH, NHC(.dbd.O), C(.dbd.O)NH, C(.dbd.O), C(.dbd.O)O, OC(.dbd.O), NHC(.dbd.S)NH, NHC(.dbd.O)NH, SO.sub.2, (OCH.sub.2 CH.sub.2).sub.s, (CH.sub.2 CH.sub.2 O).sub.s', (OCH.sub.2 CH.sub.2 CH.sub.2).sub.s", and (CH.sub.2 CH.sub.2 CH.sub.2 O).sub.t, Z is selected from the group: aryl substituted with 0-1 R.sup.10, C.sub.3-10 cycloalkyl substituted with 0-1 R.sup.10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.10 ; R.sup.6, R.sup.6a, R.sup.7, R.sup.7a, R.sup.8, R.sup.8a, R.sup.9, and R.sup.9a are independently selected at each occurrence from the group: H, .dbd.O, COOH, SO.sub.3 H, C.sub.1 -C.sub.5 alkyl substituted with 0-1 R.sup.10, aryl substituted with 0-1 R.sup.10, benzyl substituted with 0-1R.sup.10, and C.sub.1 -C.sub.5 alkoxy substituted with 0-1R.sup.10, NHC(.dbd.O)R.sup.11, C(.dbd.O)NHR.sup.11, NHC(.dbd.O)NHR.sup.11, NHR.sup.11, R.sup.11, and a bond to C.sub.h ; R.sup.10 is independently selected at each occurrence from the group: COOR.sup.11, OH, NHR.sup.11, SO.sub.3 H, aryl substituted with 0-1 R.sup.11, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.11, C.sub.1 -C.sub.5 alkyl substituted with 0-1 R.sup.12, C.sub.1 -C.sub.5 alkoxy substituted with 0-1 R.sup.12, and a bond to C.sub.h ; R.sup.11 is independently selected at each occurrence from the group: H, aryl substituted with 0-1 R.sup.12, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.12, polyalkylene glycol substituted with 0-1 R.sup.12, carbohydrate substituted with 0-1 R.sup.12, cyclodextrin substituted with 0-1 R.sup.12, amino acid substituted with 0-1 R.sup.12, and a bond to C.sub.h ; k is 0 or 1; h is 0 or 1; h' is 0or 1; s is selected from 0, 1, 2, 3, 4, and 5; s' is selected from 0, 1, 2, 3, 4, and 5; s" is selected from 0, 1, 2, 3, 4, and 5; t is selected from 0, 1, 2, 3, 4, and 5; A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.5, A.sup.6, A.sup.7, and A.sup.8 are independently selected at each occurrence from the group: NR.sup.13, NR.sup.13 R.sup.14, S, SH, S(Pg), OH, and a bond to L.sub.n ; E is a bond, CH, or a spacer group independently selected at each occurrence from the group: C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, aryl substituted with 0-3 R.sup.17, C.sub.3-10 cycloalkyl substituted with 0-3 R.sup.17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.17 ; R.sup.13, and R.sup.14 are each independently selected from the group: a bond to L.sub.n, hydrogen, C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, aryl substituted with 0-3 R.sup.17, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.17, and an electron, provided that when one of R.sup.13 or R.sup.14 is an electron, then the other is also an electron; alternatively, R.sup.13 and R.sup.14 combine to form .dbd.C(R.sup.20)(R.sup.21); R.sup.17 is independently selected at each occurrence from the group: a bond to L.sub.n, .dbd.O, F, Cl, Br, I, --CF.sub.3, --CN, --CO.sub.2 R.sup.18, --C(.dbd.O)R.sup.18, --C(.dbd.O)N(R.sup.18).sub.2, --CH.sub.2 OR.sup.18, --OC(.dbd.O)R.sup.18, --OC(.dbd.O)OR.sup.18a, --OR.sup.18, --OC(.dbd.O)N(R.sup.18).sub.2, --NR.sup.19 C(.dbd.O)R.sup.18, --NR.sup.19 C(.dbd.O)OR.sup.18a, --NR.sup.19 C(.dbd.O)N(R.sup.18).sub.2, --NR.sup.19 SO.sub.2 N(R.sup.18).sub.2, --NR.sup.19 SO.sub.2 R.sup.18a, --SO.sub.3 H, --SO.sub.2 R.sup.18a, --S(.dbd.O)R.sup.18a, --SO.sub.2 N(R.sup.18).sub.2, --N(R.sup.18).sub.2, --NHC(.dbd.S)NHR.sub.18, .dbd.NOR.sup.18, --C(.dbd.O)NHNR.sup.18 R.sup.18a, --OCH.sub.2 CO.sub.2 H, and 2-(1-morpholino)ethoxy; R.sup.18, R.sup.18a, and R.sup.19 are independently selected at each occurrence from the group: a bond to L.sub.n, H, and C.sub.1 -C.sub.6 alkyl; R.sup.20 and R.sup.21 are independently selected from the group: H, C.sub.1 -C.sub.5 alkyl, --CO.sub.2 R.sup.25, C.sub.2 -C.sub.5 1-alkene substituted with 0-3 R.sup.23, C.sub.2 -C.sub.5 1-alkyne substituted with 0-3 R.sup.23, aryl substituted with 0-3 R.sup.23, and unsaturated 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.23 ; alternatively, R.sup.20 and R.sup.21, taken together with the divalent carbon radical to which they are attached form: ##STR79## R.sup.22 and R.sup.23 are independently selected from the group: H, and R.sup.24 ; alternatively, R.sup.22, R.sup.23 taken together form a fused aromatic or a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O; R.sup.24 is independently selected at each occurrence from the group: --CO.sub.2 R.sup.25, --C(.dbd.O)N(R.sup.25).sub.2, --CH.sub.2 OR.sup.25, --OC(.dbd.O)R.sup.25, --OR.sup.25, --SO.sub.3 H, --N(R.sup.25).sub.2, and --OCH.sub.2 CO.sub.2 H; and, R.sup.25 is independently selected at each occurrence from the group: H and C.sub.1 -C.sub.3 alkyl.

21. A kit according to claim 20, wherein: Q is a peptide selected from the group: ##STR80## R.sup.1 is L-valine, D-valine, D-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n or L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n ; R.sup.2 is L-phenylalanine, D-phenylalanine, D-1-naphthylalanine, 2-aminothiazole-4-acetic acid, L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n or tyrosine, the tyrosine optionally substituted on the hydroxy group with a bond to L.sub.n ; R.sup.3 is D-valine, D-phenylalanine, or L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n ; R.sup.4 is D-phenylalanine, D-tyrosine substituted on the hydroxy group with a bond to L.sub.n, or L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n ; provided that one of R.sup.1 and R.sup.2 in each Q is substituted with a bond to L.sub.n, and further provided that when R.sup.2 is 2-aminothiazole-4-acetic acid, K is N-methylarginine; d is 1 or 2; W is independently selected at each occurrence from the group: NHC(.dbd.O), C(.dbd.O)NH, C(.dbd.O), (CH.sub.2 CH.sub.2 O).sub.s', and (CH.sub.2 CH.sub.2 CH.sub.2 O).sub.t ; R.sup.6, R.sup.6a, R.sup.7, R.sup.7a, R.sup.8, R.sup.8a, R.sup.9, and R.sup.9a are independently selected at each occurrence from the group: H, NHC(.dbd.O)R.sup.11, and a bond to C.sub.h ; k is 0; h" is selected from 0, 1, 2, and 3; g is selected from 0, 1, 2, 3, 4, and 5; g' is selected from 0, 1, 2, 3, 4, and 5; g" is selected from 0, 1, 2, 3, 4, and 5; g"' is selected from 0, 1, 2, 3, 4, and 5; s' is 1 or 2; t is 1 or 2; C.sub.h is ##STR81## A.sup.1 is selected from the group: OH, and a bond to L.sub.n ; A.sup.2, A.sup.4, and A.sup.6 are each N; A.sup.3, A.sup.5, and A.sup.8 are each OH; A.sup.7 is a bond to L.sub.n or NH-bond to L.sub.n ; E is a C.sub.2 alkyl substituted with 0-1 R.sup.17 ; R.sup.17 is .dbd.O; alternatively, C.sub.h is ##STR82## A.sup.1 is NH.sub.2 or N.dbd.C(R.sup.20)(R.sup.21); E is a bond; A.sup.2 is NHR.sup.13 ; R.sup.13 is a heterocycle substituted with R.sup.17, the heterocycle being selected from pyridine and pyrimidine; R.sup.17 is selected from a bond to L.sub.n, C(.dbd.O)NHR.sup.18, and C(.dbd.O)R.sup.18 ; R.sup.18 is a bond to L.sub.n ; R.sup.24 is selected from the group: --CO.sub.2 R.sup.25, --OR.sup.25, --SO.sub.3 H, and --N(R.sup.25).sub.2 ; R.sup.25 is independently selected at each occurrence from the group: hydrogen and methyl; ##STR83## alternatively, C.sub.h is A.sup.1, A.sup.2, A.sup.3, and A.sup.4 are each N; A.sup.5, A.sup.6, and A.sup.8 are each OH; A.sup.7 is a bond to L.sub.n ; E is a C.sub.2 alkyl substituted with 0-1 R.sup.17 ; and, R.sup.17 is .dbd.O.

22. A kit according to claim 20, wherein the compound is selected from the group consisting of: (a) cyclo{Arg-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl] -benzenesulfonic acid]-3-aminopropyl)-Val }; (b) cyclo{Arg-Gly-Asp-D-Tyr((N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl ]-benzenesulfonic acid]-18-amino-14-aza-4,7,10-oxy-15-oxo-octadecoyl)-3-aminopropyl)-Val}; (c) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{D-Tyr(3-aminopropyl)-Val-Arg-Gly-Asp})-cyclo{D-Tyr(3-amino propyl)-Val-Arg-Gly-Asp}; (d) cyclo{Arg-Gly-Asp-D-Tyr-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (e) cyclo{Arg-Gly-Asp-D-Phe-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (f) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}; (g) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Phe-Glu(cyclo{Lys-Arg-Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}; (h) cyclo{Arg-Gly-Asp-D-Nal-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (i) [2-[[[5-[carbonyl]-2-pyridinyl]-hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{(Lys-Arg-Gly-Asp-D-Nal})-cyclo{Lys-Arg-Gly-Asp-D-Nal}; (j) cyclo{Arg-Gly-Asp-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-ben zenesulfonic acid])-D-Val}; (k) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Lys-D-Val-Arg-Gly-Asp})-cyclo{Lys-D-Val-Arg-Gly-Asp}; (l) {cyclo(Arg-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]- benzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly}; (m) cyclo{D-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfon ic acid])-D-Phe-D-Asp-Gly-Arg}; (n) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{D-Lys-D-Phe-D-Asp-Gly-Arg})-cyclo{D-Lys-D-Phe-D-Asp-Gly-Ar g}; (o) cyclo{D-Phe-D-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzene sulfonic acid])-D-Asp-Gly-Arg}; (p) cyclo{N-Me-Arg-Gly-Asp-ATA-D-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono] methyl]-benzenesulfonic acid])}; (q) cyclo{Cit-Gly-Asp-D-Phe-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (r) 2-(1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecyl)acetyl-Glu( cyclo{Lys-Arg-Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}; (s) cyclo{Arg-Gly-Asp-D-Phe-Lys(DTPA)}; (t) cyclo{Arg-Gly-Asp-D-Phe-Lys}.sub.2 (DTPA); (u) cyclo{Arg-Gly-Asp-D-Tyr(N-DTPA-3-aminopropyl)-Val}; (v) cyclo{Orn(d-N-2-Imidazolinyl)-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridin yl]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (w) cyclo{Lys-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl] -benzenesulfonic acid]-3-aminopropyl)-Val}; (x) cyclo{Cys(2-aminoethyl)-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hyd razono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (y) cyclo{HomoLys-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]met hyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (z) cyclo{Orn(d-N-Benzylcarbamoyl)-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridi nyl]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (aa) cyclo{Dap(b-(2-benzimidazolylacetyl))-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2 -pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (bb) cyclo{Orn(d-N-2-Imidazolinyl)-Gly-Asp-D-Phe-Lys(N-[2-[[[5-[carbonyl]-2-pyr idinyl]hydrazono]methyl]-benzenesulfonic acid])}; (cc) cyclo{Orn(d-N-Benzylcarbamoyl)-Gly-Asp-D-Phe-Lys(N-[2-[[[5-[carbonyl]-2-py ridinyl]hydrazono]methyl]-benzenesulfonic acid])}; (dd) cyclo{Lys-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-b enzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly}; (ee) cyclo{Orn(d-N-Benzylcarbamoyl)-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridiny l]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly}; and, (ff) cyclo{Orn(d-N-2-Imidazolinyl)-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl ]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly};

or a pharmaceutically acceptable salt form thereof.

23. A kit according to claim 20, wherein the kit further comprises one or more ancillary ligands and a reducing agent.

24. A kit according to claim 23, wherein the ancillary ligands are tricine and TPPTS.

25. A kit according to claim 24, wherein the reducing agent is tin(II).

26. A therapeutic radiopharmaceutical composition according to claim 8, wherein the metal is a radioisotope selected from the group: .sup.33 P, .sup.125 I, .sup.186 Re, .sup.188 Re, .sup.153 Sm, .sup.166 Ho, .sup.177 Lu, .sup.149 Pm, .sup.90 Y, .sup.212 Bi, .sup.103 Pd, .sup.109 Pd, .sup.159 Gd, .sup.140 La, .sup.198 Au, .sup.199 Au, .sup.169 Yb, .sup.175 Yb, .sup.165 Dy, .sup.166 Dy, .sup.67 Cu, .sup.105 Rh, .sup.111 Ag, and .sup.192 Ir.

27. A therapeutic radiopharmaceutical composition according to claim 26, wherein the compound is of the formula:

wherein, Q is a peptide independently selected from the group: ##STR84## K is an L-amino acid independently selected at each occurrence from the group: arginine, citrulline, N-methylarginine, lysine, homolysine, 2-aminoethylcysteine, .delta.-2-imidazolinylornithine, .delta.-N-benzylcarbamoylornithine, and .beta.-2-benzimidazolylacetyl-1,2-diaminopropionic acid; K' is a D-amino acid independently selected at each occurrence from the group: arginine, citrulline, N-methylarginine, lysine, homolysine, 2-aminoethylcysteine, .delta.-N-2-imidazolinylornithine, .delta.-N-benzylcarbamoylornithine, and .beta.-2-benzimidazolylacetyl-1,2-diaminopropionic acid; L is independently selected at each occurrence from the group: glycine, L-alanine, and D-alanine; M is L-aspartic acid; M' is D-aspartic acid; R.sup.1 is an amino acid substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, L-valine, D-valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, 2-aminohexanoic acid, tyrosine, phenylalanine, thienylalanine, phenylglycine, cyclohexylalanine, homophenylalanine, 1-naphthylalanine, lysine, serine, ornithine, 1,2-diaminobutyric acid, 1,2-diaminopropionic acid, cysteine, penicillamine, and methionine; R.sup.2 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, 2-aminohexanoic acid, tyrosine, L-phenylalanine, D-phenylalanine, thienylalanine, phenylglycine, biphenylglycine, cyclohexylalanine, homophenylalanine, L-1-naphthylalanine, D-1-naphthylalanine, lysine, serine, ornithine, 1,2-diaminobutyric acid, 1,2-diaminopropionic acid, cysteine, penicillamine, methionine, and 2-aminothiazole-4-acetic acid; R.sup.3 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-2-aminohexanoic acid, D-tyrosine, D-phenylalanine, D-thienylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-1-naphthylalanine, D-lysine, D-serine, D-ornithine, D-1,2-diaminobutyric acid, D-1,2-diaminopropionic acid, D-cysteine, D-penicillamine, and D-methionine; R.sup.4 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-2-aminohexanoic acid, D-tyrosine, D-phenylalanine, D-thienylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-1-naphthylalanine, D-lysine, D-serine, D-ornithine, D-1,2-diaminobutyric acid, D-1,2-diaminopropionic acid, D-cysteine, D-penicillamine, D-methionine, and 2-aminothiazole-4-acetic acid; R.sup.5 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, L-valine, L-alanine, L-leucine, L-isoleucine, L-norleucine, L-2-aminobutyric acid, L-2-aminohexanoic acid, L-tyrosine, L-phenylalanine, L-thienylalanine, L-phenylglycine, L-cyclohexylalanine, L-homophenylalanine, L-1-naphthylalanine, L-lysine, L-serine, L-ornithine, L-1,2-diaminobutyric acid, L-1,2-diaminopropionic acid, L-cysteine, L-penicillamine, L-methionine, and 2-aminothiazole-4-acetic acid; provided that one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 in each Q is substituted with a bond to L.sub.n, further provided that when R.sup.2 is 2-aminothiazole-4-acetic acid, K is N-methylarginine, further provided that when R.sup.4 is 2-aminothiazole-4-acetic acid, K and K' are N-methylarginine, and still further provided that when R.sup.5 is 2-aminothiazole-4-acetic acid, K' is N-methylarginine; d is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; L.sub.n is a linking group having the formula:

and a pharmaceutically acceptable salt thereof.

28. A therapeutic radiopharmaceutical composition according to claim 27, wherein L is glycine; R.sup.1 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: L-valine, D-valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, tyrosine, phenylalanine, phenylglycine, cyclohexylalanine, homophenylalanine, lysine, ornithine, 1,2-diaminobutyric acid, and 1,2-diaminopropionic acid; R.sup.2 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, tyrosine, L-phenylalanine, D-phenylalanine, thienylalanine, phenylglycine, biphenylglycine, cyclohexylalanine, homophenylalanine, L-1-naphthylalanine, D-1-naphthylalanine, lysine, ornithine, 1,2-diaminobutyric acid, 1,2-diaminopropionic acid, and 2-aminothiazole-4-acetic acid; R.sup.3 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-tyrosine, D-phenylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-lysine, D-serine, D-ornithine, D-1,2-diaminobutyric acid, and D-1,2-diaminopropionic acid; R.sup.4 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-tyrosine, D-phenylalanine, D-thienylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-1-naphthylalanine, D-lysine, D-ornithine, D-1,2-diaminobutyric acid, D-1,2-diaminopropionic acid, and 2-aminothiazole-4-acetic acid; R.sup.5 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: L-valine, L-alanine, L-leucine, L-isoleucine, L-norleucine, L-2-aminobutyric acid, L-tyrosine, L-phenylalanine, L-thienylalanine, L-phenylglycine, L-cyclohexylalanine, L-homophenylalanine, L-1-naphthylalanine, L-lysine, L-ornithine, L-1,2-diaminobutyric acid, L-1,2-diaminopropionic acid, and 2-aminothiazole-4-acetic acid; d is selected from 1, 2, and 3; W is independently selected at each occurrence from the group: O, NH, NHC(.dbd.O), C(.dbd.O)NH, C(.dbd.O), C(.dbd.O)O, OC(.dbd.O), NHC(.dbd.S)NH, NHC(.dbd.O)NH, SO.sub.2, (OCH.sub.2 CH.sub.2).sub.s, (CH.sub.2 CH.sub.2 O).sub.s', (OCH.sub.2 CH.sub.2 CH.sub.2).sub.s", and (CH.sub.2 CH.sub.2 CH.sub.2 O).sub.t, Z is selected from the group: aryl substituted with 0-1 R.sup.10, C.sub.3-10 cycloalkyl substituted with 0-1 R.sup.10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.10 ; R.sup.6, R.sup.6a, R.sup.7, R.sup.7a, R.sup.8, R.sup.8a, R.sup.9, and R.sup.9a are independently selected at each occurrence from the group: H, .dbd.O, COOH, SO.sub.3 H, C.sub.1 -C.sub.5 alkyl substituted with 0-1 R.sup.10, aryl substituted with 0-1 R.sup.10, benzyl substituted with 0-1 R.sup.10, and C.sub.1 -C.sub.5 alkoxy substituted with 0-1 R.sup.10, NHC(.dbd.O)R.sup.11, C(.dbd.O)NHR.sup.11, NHC(.dbd.O)NHR.sup.11, NHR.sup.11, R.sup.11, and a bond to C.sub.h ; R.sup.10 is independently selected at each occurrence from the group: COOR.sup.11, OH, NHR.sup.11, SO.sub.3 H, aryl substituted with 0-1 R.sup.11, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.11, C.sub.1 -C.sub.5 alkyl substituted with 0-1 R.sup.12, C.sub.1 -C.sub.5 alkoxy substituted with 0-1 R.sup.12, and a bond to C.sub.h ; R.sup.11 is independently selected at each occurrence from the group: H, aryl substituted with 0-1 R.sup.12, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.12, polyalkylene glycol substituted with 0-1 R.sup.12, carbohydrate substituted with 0-1 R.sup.12, cyclodextrin substituted with 0-1 R.sup.12 amino acid substituted with 0-1 R.sup.12 and a bond to C.sub.h ; k is 0 or 1; h is 0 or 1; h' is 0or 1; s is selected from 0, 1, 2, 3, 4, and 5; s' is selected from 0, 1, 2, 3, 4, and 5; s" is selected from 0, 1, 2, 3, 4, and 5; t is selected from 0, 1, 2, 3, 4, and 5; A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.5, A.sup.6, A.sup.7, and A.sup.8 are independently selected at each occurrence from the group: NR.sup.13, NR.sup.13 R.sup.14, S, SH, S(Pg), OH, and a bond to L.sub.n ; E is a bond, CH, or a spacer group independently selected at each occurrence from the group: C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, aryl substituted with 0-3 R.sup.17, C.sub.3-10 cycloalkyl substituted with 0--3 R.sup.17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.17 ; R.sup.13, and R.sup.14 are each independently selected from the group: a bond to L.sub.n, hydrogen, C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, aryl substituted with 0-3 R.sup.17, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.17, and an electron, provided that when one of R.sup.13 or R.sup.14 is an electron, then the other is also an electron; alternatively, R.sup.13 and R.sup.14 combine to form .dbd.C(R.sup.20)(R.sup.21); R.sup.17 is independently selected at each occurrence from the group: a bond to L.sub.n, .dbd.O, F, Cl, Br, I, --CF.sub.3, --CN, --CO.sub.2 R.sup.18, --C(.dbd.O)R.sup.18, --C(.dbd.O)N(R.sup.18).sub.2, --CH.sub.2 OR.sup.18, --OC(.dbd.O)R.sup.18, --OC(.dbd.O)O.sup.18a, --OR.sup.18, --OC(.dbd.O)N(R.sup.18).sub.2, --NR.sup.19 C(.dbd.O)R.sup.18, --NR.sup.19 C(.dbd.O)OR.sup.18a, --NR.sup.19 C(.dbd.O)N(R.sup.18).sub.2, --NR.sup.19 SO.sub.2 N(R.sup.18).sub.2, --NR.sup.19 SO.sub.2 R.sup.18a, --SO.sub.3 H, --SO.sub.2 R.sup.18a, --S(.dbd.O)R.sup.18a, --SO.sup.2 N(R.sup.18).sub.2, --N(R.sup.18).sub.2, --NHC(.dbd.S)NHR.sup.18, .dbd.NOR.sup.18, --C(.dbd.O)NHNR.sup.18 R.sup.18a, --OCH.sub.2 CO.sub.2 H, and 2-(1-morpholino)ethoxy; R.sup.18, R.sup.18a, and R.sup.19 are independently selected at each occurrence from the group: a bond to L.sub.n, H, and C.sub.1 -C.sub.6 alkyl; R.sup.20 and R.sup.21 are independently selected from the group: H, C.sub.1 -C.sub.5 alkyl, --CO.sub.2 R.sup.25, C.sub.2 -C.sub.5 1-alkene substituted with 0-3 R.sup.23, C.sub.2 -C.sub.5 1-alkyne substituted with 0-3 R.sup.23, aryl substituted with 0-3 R.sup.23, and unsaturated 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.23 ; alternatively, R.sup.20 and R.sup.21, taken together with the divalent carbon radical to which they are attached form: ##STR87## R.sup.22 and R.sup.23 are independently selected from the group: H, and R.sup.24 ; alternatively, R.sup.22, R.sup.23 taken together form a fused aromatic or a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O; R.sup.24 is independently selected at each occurrence from the group: --CO.sub.2 R.sup.25, --C(.dbd.O)N(R.sup.25).sub.2, --CH.sub.2 OR.sup.25, --OC(.dbd.O)R.sup.25, --OR.sup.25, --SO.sub.3 H, --N(R.sup.25).sub.2, and --OCH.sub.2 CO.sub.2 H; and, R.sup.25 is independently selected at each occurrence from the group: H and C.sub.1 -C.sub.3 alkyl.

29. A therapeutic radiopharmaceutical composition according to claim 28, wherein: Q is a peptide selected from the group: ##STR88## R.sup.1 is L-valine, D-valine, D-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n or L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n ; R.sup.2 is L-phenylalanine, D-phenylalanine, D-1-naphthylalanine, 2-aminothiazole-4-acetic acid, L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n or tyrosine, the tyrosine optionally substituted on the hydroxy group with a bond to L.sub.n ; R.sup.3 is D-valine, D-phenylalanine, or L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n ; R.sup.4 is D-phenylalanine, D-tyrosine substituted on the hydroxy group with a bond to L.sub.n, or L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n ; provided that one of R.sup.1 and R.sup.2 in each Q is substituted with a bond to L.sub.n, and further provided that when R.sup.2 is 2-aminothiazole-4-acetic acid, K is N-methylarginine; d is 1 or 2; W is independently selected at each occurrence from the group: NHC(.dbd.O), C(.dbd.O)NH, C(.dbd.O), (CH.sub.2 CH.sub.2 O).sub.s', and (CH.sub.2 CH.sub.2 CH.sub.2 O).sub.t ; R.sup.6, R.sup.6a, R.sup.7, R.sup.7a, R.sup.8, R.sup.8a, R.sup.9, and R.sup.9a are independently selected at each occurrence from the group: H, NHC(.dbd.O)R.sup.11, and a bond to C.sub.h ; k is 0; h" is selected from 0, 1, 2, and 3; g is selected from 0, 1, 2, 3, 4, and 5; g' is selected from 0, 1, 2, 3, 4, and 5; g" is selected from 0, 1, 2, 3, 4, and 5; g"' is selected from 0, 1, 2, 3, 4, and 5; s' is 1 or 2; t is 1 or 2; C.sub.h is ##STR89## A.sup.1 is selected from the group: OH, and a bond to L.sub.n ; A.sup.2, A.sup.4, and A.sup.6 are each N; A.sup.3, A.sup.5, and A.sup.8 are each OH; A.sup.7 is a bond to L.sub.n or NH-bond to L.sub.n ; E is a C.sub.2 alkyl substituted with 0-1 R.sup.17 ; R.sup.17 is .dbd.O; alternatively, C.sub.h is ##STR90## A.sup.1 is NH.sub.2 or N.dbd.C(R.sup.20)(R.sup.21); E is a bond; A.sup.2 is NHR.sup.13 ; R.sup.13 is a heterocycle substituted with R.sup.17, the heterocycle being selected from pyridine and pyrimidine; R.sup.17 is selected from a bond to L.sub.n, C(.dbd.O)NHR.sup.18, and C(.dbd.O)R.sup.18 ; R.sup.18 is a bond to L.sub.n ; R.sup.24 is selected from the group: --CO.sub.2 R.sup.25, --OR.sup.25, --SO.sub.3 H, and --N(R.sup.25).sub.2 ; R.sup.25 is independently selected at each occurrence from the group: hydrogen and methyl; ##STR91## alternatively, C.sub.h is A.sup.1, A.sup.2, A.sup.3, and A.sup.4 are each N; A.sup.5, A.sup.6, and A.sup.8 are each OH; A.sup.7 is a bond to L.sub.n ; E is a C.sub.2 alkyl substituted with 0-1 R.sup.17 ; and, R.sup.17 is .dbd.O.

30. A therapeutic radiopharmaceutical composition according to claim 28, wherein the compound is selected from the group consisting of: (a) cyclo{Arg-Gly-Asp-D-Tyr(N[2-[[[5-[carbonyl-2-pyridinyl]hydrazono]methyl]-b enzenesulfonic acid]-3-aminopropyl)-Val}; (b) cyclo{Arg-Gly-Asp-D-Tyr((N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl ]-benzenesulfonic acid]-18-amino-14-aza-4,7,10-oxy-15-oxo-octadecoyl)-3-aminopropyl)-Val}; (c) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{D-Tyr(3-aminopropyl)-Val-Arg-Gly-Asp})-cyclo{D-Tyr(3-amino propyl)-Val-Arg-Gly-Asp}; (d) cyclo(Arg-Gly-Asp-D-Tyr-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (e) cyclo{Arg-Gly-Asp-D-Phe-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (f) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Lys-Arg-Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}; (g) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Phe-Glu(cyclo{Lys-Arg-Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}; (h) cyclo{Arg-Gly-Asp-D-Nal-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (i) [2-[[[5-[carbonyl]-2-pyridinyl]-hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Lys-Arg-Gly-Asp-D-Nal})-cyclo{Lys-Arg-Gly-Asp-D-Nal}; (j) cyclo{Arg-Gly-Asp-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-ben zenesulfonic acid])-D-Val}; (k) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Lys-D-Val-Arg-Gly-Asp})-cyclo{Lys-D-Val-Arg-Gly-Asp}; (l) {cyclo(Arg-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]- benzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly}; (m) cyclo{D-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfon ic acid])-D-Phe-D-Asp-Gly-Arg}; (n) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{D-Lys-D-Phe-D-Asp-Gly-Arg})-cyclo{D-Lys-D-Phe-D-Asp-Gly-Ar g}; (o) cyclo{D-Phe-D-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzene sulfonic acid])-D-Asp-Gly-Arg }; (p) cyclo{N-Me-Arg-Gly-Asp-ATA-D-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono] methyl]-benzenesulfonic acid])}; (q) cyclo{Cit-Gly-Asp-D-Phe-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (r) 2-(1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecyl)acetyl-Glu( cyclo{Lys-Arg-Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}; (s) cyclo{Arg-Gly-Asp-D-Phe-Lys(DTPA)}; (t) cyclo{Arg-Gly-Asp-D-Phe-Lys ).sub.2 (DTPA); (u) cyclo{Arg-Gly-Asp-D-Tyr(N-DTPA-3-aminopropyl)-Val}; (v) cyclo{Orn(d-N-2-Imidazolinyl)-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridin yl]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (w) cyclo{Lys-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl] -benzenesulfonic acid]-3-aminopropyl)-Val}; (x) cyclo{Cys(2-aminoethyl)-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hyd razono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (y) cyclo{HomoLys-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]met hyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (z) cyclo{Orn(d-N-Benzylcarbamoyl)-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridi nyl]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (aa) cyclo{Dap(b-(2-benzimidazolylacetyl))-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2 -pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (bb) cyclo{Orn(d-N-2-Imidazolinyl)-Gly-Asp-D-Phe-Lys(N-[2-[[[5-[carbonyl]-2-pyr idinyl]hydrazono]methyl]-benzenesulfonic acid])}; (cc) cyclo{Orn(d-N-Benzylcarbamoyl)-Gly-Asp-D-Phe-Lys(N-[2-[[[5-[carbonyl]-2-py ridinyl]hydrazono]methyl]-benzenesulfonic acid])}; (dd) cyclo{Lys-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-b enzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly}; (ee) cyclo{Orn(d-N-Benzylcarbamoyl)-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridiny l]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly}; and, (ff) cyclo{Orn(d-N-2-Imidazolinyl)-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl ]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly};

or a pharmaceutically acceptable salt form thereof.

31. A therapeutic radiopharmaceutical composition according to claim 27, which further comprises one or more ancillary ligands and a reducing agent.

32. A therapeutic radiopharmaceutical composition according to claim 31, wherein the ancillary ligands are tricine and TPPTS.

33. A therapeutic radiopharmaceutical composition according to claim 32, wherein the reducing agent is tin(II).

34. A method of treating cancer according to claim 11, wherein the compound is of the formula:

wherein, Q is a peptide independently selected from the group: ##STR92## K is an L-amino acid independently selected at each occurrence from the group: arginine, citrulline, N-methylarginine, lysine, homolysine, 2-aminoethylcysteine, .delta.-N-2-imidazolinylornithine, .delta.-N-benzylcarbamoylornithine, and .beta.-2-benzimidazolylacetyl-1,2-diaminopropionic acid; K' is a D-amino acid independently selected at each occurrence from the group: arginine, citrulline, N-methylarginine, lysine, homolysine, 2-aminoethylcysteine, .delta.-N-2-imidazolinylornithine, .delta.-N-benzylcarbamoylornithine, and .beta.-2-benzimidazolylacetyl-1,2-diaminopropionic acid; L is independently selected at each occurrence from the group: glycine, L-alanine, and D-alanine; M is L-aspartic acid; M' is D-aspartic acid; R.sup.1 is an amino acid substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, L-valine, D-valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, 2-aminohexanoic acid, tyrosine, phenylalanine, thienylalanine, phenylglycine, cyclohexylalanine, homophenylalanine, 1-naphthylalanine, lysine, serine, ornithine, 1,2-diaminobutyric acid, 1,2-diaminopropionic acid, cysteine, penicillamine, and methionine; R.sup.2 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, 2-aminohexanoic acid, tyrosine, L-phenylalanine, D-phenylalanine, thienylalanine, phenylglycine, biphenylglycine, cyclohexylalanine, homophenylalanine, L-1-naphthylalanine, D-1-naphthylalanine, lysine, serine, ornithine, 1,2-diaminobutyric acid, 1,2-diaminopropionic acid, cysteine, penicillamine, methionine, and 2-aminothiazole-4-acetic acid; R.sup.3 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-2-aminohexanoic acid, D-tyrosine, D-phenylalanine, D-thienylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-1-naphthylalanine, D-lysine, D-serine, D-ornithine, D-1,2-diaminobutyric acid, D-1,2-diaminopropionic acid, D-cysteine, D-penicillamine, and D-methionine; R.sup.4 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-2-aminohexanoic acid, D-tyrosine, D-phenylalanine, D-thienylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-1-naphthylalanine, D-lysine, D-serine, D-ornithine, D-1,2-diaminobutyric acid, D-1,2-diaminopropionic acid, D-cysteine, D-penicillamine, D-methionine, and 2-aminothiazole-4-acetic acid; R.sup.5 is an amino acid, substituted with 0-1 bonds to L.sub.n, independently selected at each occurrence from the group: glycine, L-valine, L-alanine, L-leucine, L-isoleucine, L-norleucine, L-2-aminobutyric acid, L-2-aminohexanoic acid, L-tyrosine, L-phenylalanine, L-thienylalanine, L-phenylglycine, L-cyclohexylalanine, L-homophenylalanine, L-1-naphthylalanine, L-lysine, L-serine, L-ornithine, L-1,2-diaminobutyric acid, L-1,2-diaminopropionic acid, L-cysteine, L-penicillamine, L-methionine, and 2-aminothiazole-4-acetic acid; provided that one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 in each Q is substituted with a bond to L.sub.n, further provided that when R.sup.2 is 2-aminothiazole-4-acetic acid, K is N-methylarginine, further provided that when R.sup.4 is 2-aminothiazole-4-acetic acid, K and K' are N-methylarginine, and still further provided that when R.sup.5 is 2-aminothiazole-4-acetic acid, K' is N-methylarginine; d is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; L.sub.n is a linking group having the formula:

and a pharmaceutically acceptable salt thereof.

35. A method of treating cancer according to claim 34, wherein L is glycine; R.sup.1 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: L-valine, D-valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, tyrosine, phenylalanine, phenylglycine, cyclohexylalanine, homophenylalanine, lysine, ornithine, 1,2-diaminobutyric acid, and 1,2-diaminopropionic acid; R.sup.2 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: valine, alanine, leucine, isoleucine, norleucine, 2-aminobutyric acid, tyrosine, L-phenylalanine, D-phenylalanine, thienylalanine, phenylglycine, biphenylglycine, cyclohexylalanine, homophenylalanine, L-1-naphthylalanine, D-1-naphthylalanine, lysine, ornithine, 1,2-diaminobutyric acid, 1,2-diaminopropionic acid, and 2-aminothiazole-4-acetic acid; R.sup.3 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-tyrosine, D-phenylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-lysine, D-serine, D-ornithine, D-1,2-diaminobutyric acid, and D-1,2-diaminopropionic acid; R.sup.4 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: D-valine, D-alanine, D-leucine, D-isoleucine, D-norleucine, D-2-aminobutyric acid, D-tyrosine, D-phenylalanine, D-thienylalanine, D-phenylglycine, D-cyclohexylalanine, D-homophenylalanine, D-1-naphthylalanine, D-lysine, D-ornithine, D-1,2-diaminobutyric acid, D-1,2-diaminopropionic acid, and 2-aminothiazole-4-acetic acid; R.sup.5 is an amino acid, optionally substituted with a bond to L.sub.n, independently selected at each occurrence from the group: L-valine, L-alanine, L-leucine, L-isoleucine, L-norleucine, L-2-aminobutyric acid, L-tyrosine, L-phenylalanine, L-thienylalanine, L-phenylglycine, L-cyclohexylalanine, L-homophenylalanine, L-1-naphthylalanine, L-lysine, L-ornithine, L-1,2-diaminobutyric acid, L-1,2-diaminopropionic acid, and 2-aminothiazole-4-acetic acid; d is selected from 1, 2, and 3; W is independently selected at each occurrence from the group: O, NH, NHC(.dbd.O), C(.dbd.O)NH, C(.dbd.O), C(.dbd.O)O, OC(.dbd.O), NHC(.dbd.S)NH, NHC(.dbd.O)NH, SO.sub.2, (OCH.sub.2 CH.sub.2).sub.s, (CH.sub.2 CH.sub.2 O).sub.s', (OCH.sub.2 CH.sub.2 CH.sub.2).sub.s", and (CH.sub.2 CH.sub.2 CH.sub.2 O).sub.t, Z is selected from the group: aryl substituted with 0-1 R.sup.10, C.sub.3-10 cycloalkyl substituted with 0-1 R.sup.10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.10 ; R.sup.6, R.sup.6a, R.sup.7, R.sup.7a, R.sup.8, R.sup.8a, R.sup.9, and R.sup.9a are independently selected at each occurrence from the group: H, .dbd.O, COOH, SO.sub.3 H, C.sub.1 -C.sub.5 alkyl substituted with 0-1 R.sup.10, aryl substituted with 0-1 R.sup.10, benzyl substituted with 0-1 R.sup.10, and C.sub.1 -C.sub.5 alkoxy substituted with 0-1 R.sup.10, NHC(.dbd.O)R.sup.11, C(.dbd.O)NHR.sup.11, NHC(.dbd.O)NHR.sup.11, NHR.sup.11, R.sup.11, and a bond to C.sub.h ; R.sup.10 is independently selected at each occurrence from the group: COOR.sup.11, OH, NHR.sup.11, SO.sub.3 H, aryl substituted with 0-1 R.sup.11, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.11, C.sub.1 -C.sub.5 alkyl substituted with 0-1 R.sup.12, C.sub.1 -C.sub.5 alkoxy substituted with 0-1 R.sup.12, and a bond to C.sub.h ; R.sup.11 is independently selected at each occurrence from the group: H, aryl substituted with 0-1 R.sup.12, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.12, polyalkylene glycol substituted with 0-1 R.sup.12, carbohydrate substituted with 0-1 R.sup.12, cyclodextrin substituted with 0-1 R.sup.12, amino acid substituted with 0-1 R.sup.12, and a bond to C.sub.h ; k is 0 or 1; h is 0 or 1; h' is 0or 1; s is selected from 0, 1, 2, 3, 4, and 5; s' is selected from 0, 1, 2, 3, 4, and 5; s" is selected from 0, 1, 2, 3, 4, and 5; t is selected from 0, 1, 2, 3, 4, and 5; A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.5, A.sup.6, A.sup.7, and A.sup.8 are independently selected at each occurrence from the group: NR.sup.13, NR.sup.13 R.sup.14, S, SH, S(Pg), OH, and a bond to L.sub.n ; E is a bond, CH, or a spacer group independently selected at each occurrence from the group: C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, aryl substituted with 0-3 R.sup.17, C.sub.3-10 cycloalkyl substituted with 0-3 R.sup.17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.17 ; R.sup.13, and R.sup.14 are each independently selected from the group: a bond to L.sub.n, hydrogen, C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, aryl substituted with 0-3 R.sup.17, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.17, and an electron, provided that when one of R.sup.13 or R.sup.14 is an electron, then the other is also an electron; alternatively, R.sup.13 and R.sup.14 combine to form .dbd.C(R.sup.20)(R.sup.21); R.sup.17 is independently selected at each occurrence from the group: a bond to L.sub.n, .dbd.O, F, Cl, Br, I, --CF.sub.3, --CN, --CO.sub.2 R.sup.18, --C(.dbd.O)R.sup.18, --C(.dbd.O)N(R.sup.18).sub.2, --CH.sub.2 OR.sup.18, --OC(.dbd.O)R.sup.18, --OC(.dbd.O)OR.sup.18a, --OR.sup.18, --OC(.dbd.O)N(R.sup.18).sub.2, --NR.sup.19 C(.dbd.O)R.sup.18, --NR.sup.19 C(.dbd.O)OR.sup.18a, --NR.sup.19 C(.dbd.O)N(R.sup.18).sub.2, --NR.sup.19 SO.sub.2 N(R.sup.18).sub.2, --NR.sup.19 SO.sub.2 R.sup.18a, --SO.sub.3 H, --SO.sup.2 R.sup.18a, --S(.dbd.O)R.sup.18a, --SO.sub.2 N(R.sup.18).sub.2, --N(R.sup.18).sub.2, --NHC(.dbd.S)NHR.sup.18, .dbd.NOR.sup.18, --C(.dbd.O)NHNR.sup.18 R.sup.18a, --OCH.sub.2 CO.sub.2 H, and 2-(1-morpholino)ethoxy; R.sup.18, R.sup.18a, and R.sup.19 are independently selected at each occurrence from the group: a bond to L.sub.n, H, and C.sub.1 -C.sub.6 alkyl; R.sup.20 and R.sup.21 are independently selected from the group: H, C.sub.1 -C.sub.5 alkyl, --CO.sub.2 R.sup.25, C.sub.2 -C.sub.5 1-alkene substituted with 0-3 R.sup.23, C.sub.2 -C.sub.5 1-alkyne substituted with 0-3 R.sup.23, aryl substituted with 0-3 R.sup.23, and unsaturated 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.23 ; alternatively, R.sup.20 and R.sup.21, taken together with the divalent carbon radical to which they are attached form: ##STR95## R.sup.22 and R.sup.23 are independently selected from the group: H, and R.sup.24 ; alternatively, R.sup.22, R.sup.23 taken together form a fused aromatic or a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O; R.sup.24 is independently selected at each occurrence from the group: --CO.sub.2 R.sup.25, --C(.dbd.O)N(R.sup.25).sub.2, --CH.sub.2 OR.sup.25, --OC(.dbd.O)R.sup.25, --OR.sup.25, --SO.sub.3 H, --N(R.sup.25).sub.2, and --OCH.sub.2 CO.sub.2 H; and, R.sup.25 is independently selected at each occurrence from the group: H and C.sub.1 -C.sub.3 alkyl.

36. A method of treating cancer according to claim 35, wherein: Q is a peptide selected from the group: ##STR96## R.sup.1 is L-valine, D-valine, D-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n or L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n ; R.sup.2 is L-phenylalanine, D-phenylalanine, D-1-naphthylalanine, 2-aminothiazole-4-acetic acid, L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n or tyrosine, the tyrosine optionally substituted on the hydroxy group with a bond to L.sub.n ; R.sup.3 is D-valine, D-phenylalanine, or L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n ; R.sup.4 is D-phenylalanine, D-tyrosine substituted on the hydroxy group with a bond to L.sub.n, or L-lysine optionally substituted on the .epsilon. amino group with a bond to L.sub.n ; provided that one of R.sup.1 and R.sup.2 in each Q is substituted with a bond to L.sub.n, and further provided that when R.sup.2 is 2-aminothiazole-4-acetic acid, K is N-methylarginine; d is 1 or 2; W is independently selected at each occurrence from the group: NHC(.dbd.O), C(.dbd.O)NH, C(.dbd.O), (CH.sub.2 CH.sub.2 O).sub.s', and (CH.sub.2 CH.sub.2 CH.sub.2 O).sub.t ; R.sup.6, R.sup.6a, R.sup.7, R.sup.7a, R.sup.8, R.sup.8a, R.sup.9, and R.sup.9a are independently selected at each occurrence from the group: H, NHC(.dbd.O)R.sup.11, and a bond to C.sub.h ; k is 0; h" is selected from 0, 1, 2, and 3; g is selected from 0, 1, 2, 3, 4, and 5; g' is selected from 0, 1, 2, 3, 4, and 5; g" is selected from 0, 1, 2, 3, 4, and 5; g"' is selected from 0, 1, 2, 3, 4, and 5; s' is 1 or 2; t is 1 or 2; C.sub.h is ##STR97## A.sup.1 is selected from the group: OH, and a bond to L.sub.n ; A.sup.2, A.sup.4, and A.sup.6 are each N; A.sup.3, A.sup.5, and A.sup.8 are each OH; A.sup.7 is a bond to L.sub.n or NH-bond to L.sub.n ; E is a C.sub.2 alkyl substituted with 0-1 R.sup.17 ; R.sup.17 is .dbd.O; alternatively, C.sub.h is ##STR98## A.sup.1 is NH.sub.2 or N.dbd.C(R.sup.20)(R.sup.21); E is a bond; A.sup.2 is NHR.sup.13 ; R.sup.13 is a heterocycle substituted with R.sup.17, the heterocycle being selected from pyridine and pyrimidine; R.sup.17 is selected from a bond to L.sub.n, C(.dbd.O)NHR.sup.18, and C(.dbd.O)R.sup.18 ; R.sup.18 is a bond to L.sub.n ; R.sup.24 is selected from the group: --CO.sub.2 R.sup.25, --OR.sup.25, --SO.sub.3 H, and --N(R.sup.25).sub.2 ; R.sup.25 is independently selected at each occurrence from the group: hydrogen and methyl; ##STR99## alternatively, C.sub.h is A.sup.1, A.sup.2, A.sup.3, and A.sup.4 are each N; A.sup.5, A.sup.6, and A.sup.8 are each OH; A.sup.7 is a bond to L.sub.n ; E is a C.sub.2 alkyl substituted with 0-1 R.sup.17 ; and, R.sup.17 is .dbd.O.

37. A method of treating cancer according to claim 34, wherein the compound is selected from the group consisting of: (a) cyclo{Arg-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl] -benzenesulfonic acid]-3-aminopropyl)-Val}; (b) cyclo{Arg-Gly-Asp-D-Tyr((N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl ]-benzenesulfonic acid]-18-amino-14-aza-4,7,10-oxy-15-oxo-octadecoyl)-3-aminopropyl)-Val}; (c) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{D-Tyr(3aminopropyl)-Val-Arg-Gly-Asp})-cyclo{D-Tyr(3-aminop ropyl)-Val-Arg-Gly-Asp}; (d) cyclo(Arg-Gly-Asp-D-Tyr-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (e) cyclo{Arg-Gly-Asp-D-Phe-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (f) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Lys-Arg-Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}; (g) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Phe-Glu(cyclo{Lys-Arg-Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}; (h) cyclo{Arg-Gly-Asp-D-Nal-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (i) [2-[[[5-[carbonyl]-2-pyridinyl]-hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Lys-Arg-Gly-Asp-D-Nal})-cyclo{Lys-Arg-Gly-Asp-D-Nal}; (j) cyclo{Arg-Gly-Asp-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-ben zenesulfonic acid])-D-Val}; (k) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Lys-D-Val-Arg-Gly-Asp})-cyclo{Lys-D-Val-Arg-Gly-Asp}; (l) {cyclo(Arg-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]- benzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly}; (m) cyclo{D-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfon ic acid])-D-Phe-D-Asp-Gly-Arg}; (n) [2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{D-Lys-D-Phe-D-Asp-Gly-Arg})-cyclo{D-Lys-D-Phe-D-Asp-Gly-Ar g}; (o) cyclo{D-Phe-D-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-benzene sulfonic acid])-D-Asp-Gly-Arg}; (p) cyclo{N-Me-Arg-Gly-Asp-ATA-D-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono] methyl]-benzenesulfonic acid])}; (q) cyclo{Cit-Gly-Asp-D-Phe-Lys([2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methy l]-benzenesulfonic acid])}; (r) 2-(1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecyl)acetyl-Glu( cyclo{Lys-Arg-Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}; (s) cyclo{Arg-Gly-Asp-D-Phe-Lys(DTPA)}; (t) cyclo{Arg-Gly-Asp-D-Phe-Lys}.sub.2 (DTPA); (u) Cyclo{Arg-Gly-Asp-D-Tyr(N-DTPA-3-aminopropyl)-Val}; (v) cyclo{Orn(d-N-2-Imidazolinyl)-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridin yl]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (w) cyclo{Lys-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl] -benzenesulfonic acid]-3-aminopropyl)-Val}; (x) cyclo{Cys(2-aminoethyl)-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hyd razono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val }; (y) cyclo{HomoLys-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]met hyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (z) cyclo{Orn(d-N-Benzylcarbamoyl)-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridi nyl]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (aa) cyclo{Dap(b-(2-benzimidazolylacetyl))-Gly-Asp-D-Tyr(N-[2-[[[5-[carbonyl]-2 -pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-Val}; (bb) cyclo{Orn(d-N-2-Imidazolinyl)-Gly-Asp-D-Phe-Lys(N-[2-[[[5-[carbonyl]-2-pyr idinyl]hydrazono]methyl]-benzenesulfonic acid])}; (cc) cyclo{Orn(d-N-Benzylcarbamoyl)-Gly-Asp-D-Phe-Lys(N-[2-[[[5-[carbonyl]-2-py ridinyl]hydrazono]methyl]-benzenesulfonic acid])}; (dd) cyclo{Lys-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl]hydrazono]methyl]-b enzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly}; (ee) cyclo{Orn(d-N-Benzylcarbamoyl)-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridiny l]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly}; and, (ff) cyclo{Orn(d-N-2-Imidazolinyl)-D-Val-D-Tyr(N-[2-[[[5-[carbonyl]-2-pyridinyl ]hydrazono]methyl]-benzenesulfonic acid]-3-aminopropyl)-D-Asp-Gly};

or a pharmaceutically acceptable salt form thereof.

Details for Patent 6,537,520

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Eisai Inc ONTAK denileukin diftitox VIAL 103767 001 1999-02-05   Request a Trial Bristol-Myers Squibb Pharma Company (Princeton, NJ) 2018-03-31 RX Orphan search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

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