Radiolabeled alpha-melanocyte stimulating hormone hybrid peptide for melanoma targeting

Patent metadata

Field	Value
Publication number	US-10238758-B2
Application number	US-201615261890-A
Country	US
Kind code	B2
Filing date	Sep 10, 2016
Priority date	Sep 29, 2011
Publication date	Mar 26, 2019
Grant date	Mar 26, 2019

Abstract

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, suggesting favorable selective activity of compounds according to the present invention, which can be used as effective therapeutic agents against melanoma, including metastatic melanoma. 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 useful to initiate 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 and therapeutic tools for a number of conditions and diseases states, especially melanoma.

First claim

The invention claimed is:

1. A compound according to the chemical structure:

Where Q, V and W are each independently an amino acid unit selected from the group consisting of glutamic acid and aspartic acid;
R is an amino acid unit selected from the group consisting of valine, threonine, leucine, and isoleucine;
X is an amino acid residue selected from the group consisting of alanine, valine, threonine, leucine, isoleucine and serine;
Y is an amino acid residue selected from the group consisting of aspartic acid and glutamic acid;
L is alanine or a linker group according to the structure:

p is an integer from 0 to 20;
k is an integer from 1 to 10;
i is 1 or 2;
s is 0, 1 or 2; and
M is a radioisotope, or
a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein said radioisotope is a polyvalent cationic radioisotope selected from the group consisting of 86 Y, 90 Y, 111 In, 177 Lu, 225 Ac, 212 Bi, 213 Bi, 66 Ga, 67 Ga, 68 Ga, 64 Cu, 67 Cu, 71 As, 72 As, 76 As, 77 As, 65 Zn, 48 V, 203 Pb, 209 Pb, 212 Pb, 166 Ho, 149 Pm, 153 Sm, 201 Tl, 188 Re, 186 Re, and 99m Tc.

3. The compound according to claim 1 wherein X is alanine.

4. The compound according to claim 1 wherein said compound is

Where Q is glutamic acid;
R is valine;
V is aspartic acid;
W is aspartic acid;
X is alanine, valine, threonine, leucine or isoleucine;
Y is aspartic acid or glutamic acid;
p is an integer from 0-6;
k is 1 or 2;
i is 1;
s is 0; and
M is 99m Tc, 188 Re or 186 Re; or
a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 wherein L is

and p is 1-6.

6. The compound according to claim 1 wherein L is

s is 0 and i is 1; and
k is 1-5.

7. The compound according to claim 1 wherein M is 99m Tc, 188 Re or 186 Re.

8. A method of diagnosing melanoma in a patient suspected of having melanoma comprising administering to said patient an effective amount of a compound according to claim 1 and determining whether said compound has bound to tissue in said patient which evidences the existence of a melanoma tumor in said tissue when compared to a standard.

9. The method according to claim 8 wherein said radioisotope M is a polyvalent cationic radioisotope selected from the group consisting of 86 Y, 90 Y, 111 In, 177 Lu, 225 Ac, 212 Bi, 213 Bi, 66 Ga, 67 Ga, 68 Ga, 64 Cu, 67 Cu, 71 As, 72 As, 76 As, 77 As, 65 Zn, 48 V, 203 Pb, 209 Pb, 212 Pb, 166 Ho, 149 Pm, 153 Sm, 201 Tl, 188 Re, 186 Re, and 99m Tc.

10. The method according to claim 8 wherein X is alanine.

11. A method of treating melanoma in a patient in need thereof comprising administering to said patient an effective amount of a compound according to claim 1 , wherein said radioisotope is 90 Y, 177 Lu, 225 Ac, 212 Bi, 213 Bi, 66 Ga, 67 Cu, 212 Pb, 166 Ho, 149 Pm, 153 Sm, 188 Re, 186 Re, 76 As or 77 As.

12. The method according to claim 11 wherein said compound is administered in topical dosage form.

13. The method according to claim 12 wherein said compound is administered directly onto melanoma tissue on the skin.

14. The method according to claim 11 wherein said compound is administered in parenteral dosage form.

15. The method according to claim 11 wherein said melanoma is metastatic melanoma.

16. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 in combination with a pharmaceutically acceptable carrier, additive or excipient.

17. The composition according to claim 16 in topical dosage form.

18. The composition according to claim 16 in parenteral dosage form.

19. A method of monitoring melanoma treatment in a patient being treated for melanoma comprising administering a compound according to claim 1 to said patient, and diagnosing melanoma in said patient during the course of said treatment by measuring the extent of binding of said compound to melanoma tissue in said patient, wherein a decrease in melanoma tissue evidenced by reduced binding of said compound to said melanoma tissue in said patient during the course of said treatment is evidence of success of said treatment.

Assignees

• Stc Unm

Inventors

• Miao Yubin

Classifications

• A61K38/17

  from animals; from humans {(enzyme inhibitors A61K38/005)} · CPC title

• A61K51/082

  the peptide being a RGD-containing peptide · CPC title

• C07K7/56

  the cyclisation not occurring through 2,4-diamino-butanoic acid · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K51/086 Primary

  the peptide being alphaMSH, alpha melanocyte stimulating hormone · CPC title