Small technetium-99m and rhenium labeled agents and methods for imaging tumors

• US 7,321,027 B2
• Filed: 10/23/2002
• Issued: 01/22/2008
• Est. Priority Date: 04/28/2000
• Status: Expired due to Fees

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation), Massachusetts Institute of Technology
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation), Massachusetts Institute of Technology
• Inventors: Bolzati, Cristina, Davison, Alan, Mahmood, Ashfaq, Jones, Alun G., Friebe, Matthias
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US10/279,214
• Publication Number:
  US 20040097735A1
• Time in Patent Office: 1,917 Days
• Field of Search: 424/1.11, 424/1.65, 424/9.1, 534/7, 534 10- 16, 546/1, 514/183
• US Class Current: 534/14
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07C 323/41 Y being a hydrogen or an acyclic carbon atom
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain
• CPC Class Codes: C07F 13/005 Compounds without a metal-carbon linkage
• CPC Class Codes: C07K 5/06026 the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala

Abstract

The present invention relates to compounds and related technetium and rhenium complexes thereof which are suitable for imaging or therapeutic treatment of tumors, e.g., carcinomas, melanomas and other tumors. In another embodiment, the invention relates to methods of imaging tumors using radiolabeled metal complexes. Preferred radiolabeled complexes for imaging tumors include technetium and rhenium complexes. The high tumor uptake and significant tumor/nontumor ratios of the technetium complexes of the invention indicate that such small technetium-99m-based molecular probes can be developed as in-vivo diagnostic agents for melanoma and its metastases. In yet another embodiment, the invention relates to methods of treatment of tumors using a radiolabeled metal complex as a radiopharmaceutical agent to treat the tumor.

Claims

1. A compound represented by the formula:

2. The compound of claim 1, wherein the compound is capable of binding a metal ion selected from the group consisting of technetium, rhenium, yttrium, copper, gallium, indium, bismuth, platinum and rhodium.

3. The compound of claim 1, wherein the compound is capable of binding technetium or rhenium.

6. A neutral or cationic radiolabeled complex comprising a metal ion and a compound that binds the metal ion, wherein the compound is a compound of claim 1.

7. The neutral or cationic radiolabeled complex of claim 6, wherein the metal ion is selected from the group consisting of technetium, rhenium, yttrium, copper, gallium, indium, bismuth, platinum and rhodium.

8. The neutral or cationic radiolabeled complex of claim 6, wherein the metal ion is technetium-99m or one or more isotopes of rhenium.

13. A method for in-vivo or in-vitro imaging of at least one tumor comprising the steps of:

(a) providing a radiolabeled neutral or cationic radiolabeled complex comprising a metal ion and a compound that binds the metal ion, wherein the compound is a compound according to claim 1.

14. The method of claim 13, wherein the metal ion is technetium-99m or one or more isotopes of rhenium.

15. The method of claim 13, wherein the tumor(s) are neoplasm(s).

16. The method of claim 13, wherein the tumor(s) are carcinoma(s).

17. The method of claim 13, wherein the tumor(s) are melanoma(s).

18. A method for the treatment of cancer comprising the steps of:

(a) providing a cytotoxic metal complex comprising a metal ion and a compound that binds the metal ion, wherein the compound is a compound according to claim 1; and

(b) contacting the tumor(s) with the cytotoxic metal complex.

19. A method of claim 18, wherein the metal ion is a radioactive isotope of technetium, rhenium, yttrium, copper, gallium, indium, bismuth, platinum, or rhodium.

4. A compound represented by the formula:

9. A neutral or cationic radiolabeled complex comprising a metal ion and a compound that binds the metal ion, wherein the compound a compound of claim 4.

5. A compound represented by the formula:

10. A neutral or cationic radiolabeled complex comprising a metal ion and a compound that binds the metal ion, wherein the compound is a compound of claim 5.

11. A neutral or cationic radiolabeled complex of the formula:

12. A neutral or cationic radiolabeled complex of the formula: