Compounds with reduced ring size for use in diagnosing and treating melanoma, including metastatic melanoma and methods related to same
The present invention is directed to novel non-invasive diagnostic tools/compounds to image cancers, especially, melanoma, including metastatic melanoma in vivo. The present compounds exhibit enhanced uptake in cancerous cells and tissue and decreased renal uptake in kidney, evidencing favorable pharmacokinetics of compounds of the present invention. The compounds according to the present invention represent an advance in the diagnosis and treatment of melanoma, including metastatic melanoma using non-invasive molecular imaging techniques. The novel probes of the present invention are also useful for initiating therapy for melanoma as well as monitor patients' response to chemotherapy treatments and other interventions or therapies used in the treatment of melanoma/metastatic melanoma. Compounds according to the present invention may be used as diagnostic tools for a number of conditions and diseases states as well as therapeutic agents for treating such conditions and disease states.
1. A compound according to the chemical structure:
wherein Y 1 is a DOTA group, a NOTA group or a HYNIC group;
X is GlyGlyNle or X is X′ m -(ABC) n where X′ is
A is absent,
B is Nle,
C is absent,
m is 1,
n is 1 and
p is 7, or
a pharmaceutically acceptable salt thereof,
wherein said compound is optionally complexed with at least one radioisotope selected from the group consisting of 111 In, 177 Lu, 67 Ga, 64 Cu, and 99m Tc.
2. The compound according to claim 1 complexed with a radioisotope.
3. The compound according to claim 1 wherein Y′ is a DOTA group, X is GlyGlyNle and said compound is complexed with a radioisotope selected from the group consisting of 111 In and 177 Lu.
4. The compound according to claim 1 wherein Y 1 is a NOTA group, X is GlyGlyNle and said compound is complexed with a radioisotope selected from the group consisting of 67 Ga and 64 Cu.
5. The compound according to claim 1 wherein Y 1 is a HYNIC group, X is GlyGlyNle or X′ m -(ABC) n where X′ is
A is absent, B is Nle, C is absent and m is 1 and n is 1 and said compound is complexed with a radioisotope which is 99m Tc.
6. A pharmaceutical composition comprising an effective amount of a compound comprising a radioisotope according to claim 1 in combination with a pharmaceutically acceptable carrier, additive or excipient.
7. A pharmaceutical composition comprising an effective amount of a compound according to claim 2 in combination with a pharmaceutically acceptable carrier, additive or excipient.
8. A pharmaceutical composition comprising an effective amount of a compound according to claim 3 in combination with a pharmaceutically acceptable carrier, additive or excipient.
9. A pharmaceutical composition comprising an effective amount of a compound according to claim 4 in combination with a pharmaceutically acceptable carrier, additive or excipient.
10. A pharmaceutical composition comprising an effective amount of a compound according to claim 5 in combination with a pharmaceutically acceptable carrier, additive or excipient.
11. The compound according to claim 3 wherein said radioisotope is 111 In.
12. The compound according to claim 3 wherein said radioisotope is 177 Lu.
13. The compound according to claim 4 wherein said radioisotope is 67 Ga.
14. The compound according to claim 4 wherein said radioisotope is 64 Cu.
15. The compound according to claim 5 wherein X is GlyGlyNle.
16. The compound according to claim 5 wherein X is X′ m -(ABC) n .
17. A pharmaceutical composition comprising an effective amount of a compound according to claim 11 in combination with a pharmaceutically acceptable carrier, additive or excipient.
18. A pharmaceutical composition comprising an effective amount of a compound according to claim 12 in combination with a pharmaceutically acceptable carrier, additive or excipient.
19. A pharmaceutical composition comprising an effective amount of a compound according to claim 13 in combination with a pharmaceutically acceptable carrier, additive or excipient.
20. A pharmaceutical composition an effective amount of a compound according to claim 14 in combination with a pharmaceutically acceptable carrier, additive or excipient.
21. A pharmaceutical composition comprising an effective amount of a compound according to claim 15 in combination with a pharmaceutically acceptable carrier, additive or excipient.
22. A pharmaceutical composition comprising an effective amount of a compound according to claim 16 in combination with a pharmaceutically acceptable carrier, additive or excipient.