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Claims for Patent: 4,452,774

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Claims for Patent: 4,452,774

Title: Isonitrile radionuclide complexes for labelling and imaging agents
Abstract:A coordination complex of an isonitrile ligand and radionuclide such as Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta, is useful as a diagnostic agent for labelling liposomes or vesicles, and selected living cells containing lipid membranes, such as blood clots, myocardial tissue, gall bladder tissue, etc.
Inventor(s): Jones; Alun G. (Newton Centre, MA), Davison; Alan (Needham, MA), Abrams; Michael J. (Allston, MA)
Assignee: President and Fellows of Harvard College (Cambridge, MA) Massachusetts Institute of Technology (Cambridge, MA)
Application Number:06/373,511
Patent Claims: 1. A coordination complex of an isonitrile ligand and a radioactive metal selected from the class consisting of radioactive isotopes of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb, and Ta.

2. A complex as claimed in claim 1 in which said metal is Tc.

3. A complex as claimed in claim 1 in which said metal is Re.

4. A complex as claimed in claim 1, 2 or 3 in which said isonitrile ligand is aliphatic.

5. A complex as claimed in claim 1, 2 or 3 in which said isonitrile ligand is a hydrocarbon isonitrile.

6. A complex as claimed in claim 1, 2 or 3 in which said isonitrile ligand is a saturated hydrocarbon isonitrile.

7. A complex as claimed in claim 1 wherein each coordinate position of said radioactive metal is filled by an isonitrile ligand.

8. A complex as claimed in claim 1 wherein said isonitrile ligand is a monodentate ligand.

9. A complex as claimed in claim 1 wherein said isonitrile ligand is a bidentate ligand.

10. A complex as claimed in claim 1 wherein said isonitrile ligand is a tridentate ligand.

11. A complex as claimed in claim 1 wherein said complex is a cationic lipophilic complex.

12. A complex as claimed in claim 1 wherein said radioactive metal is a radioactive isotope of Tc, Ru, Co, Pt, Fe, Os or Ir.

13. A complex as claimed in claim 1 wherein said radioactive metal is a radioactive isotope of W, Re, Fe or Os.

14. A complex as claimed in claim 1 wherein said radioactive metal is a radioactive isotope of Cr, Mo, Co, Tc, Fe, Mn, W, Ru, Ni, Rh, Ir, Pd, Nb or Ta.

15. An isonitrile complex having the formula:

wherein A is a radionuclide selected from radioactive isotopes of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Ta; (CN).sub.x R is a monodentate or polydentate isonitrile ligand bonded to the radionuclide through the carbon atom of the CN group; R is an organic radical; B and B' are independently other ligands selected from the class of solvents, halogen groups, and ligands comprising one or more neutral donor atoms capable of forming coordinant bonds with said radionuclide; x and y are each independently, integers from 1 to 8; z and z' are each independently 0 or an integer from 1 to 7; with the proviso that (xy)+z+z' is less than or equal to 8; and n indicates the charge of the complex and can be 0 (neutral), or a positive or negative integer.

16. An isontrile complex having the formula;

wherein A is a radionuclide selected from technetium and .sup.188 Re, and R is an organic radical.

17. A cationic lipophilic hexakis t-butylisonitrile complex of technetium.

18. A kit for preparing a coordination complex of an isonitrile ligand and a radionuclide selected from the class consisting of radioactive isotope of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta, said kit comprising a predetermined quantity of said isonitrile ligand and a predetermined quantity of a reducing agent capable of reducing a predetermined quantity of a preselected one of said radionuclides to form said complex.

19. A kit as claimed in claim 18 wherein said isonitrile ligand and said reducing agent are lyophilized.

20. A kit as claimed in claim 18 wherein said lyophilized isonitrile ligand and reducing agent are contained in a sealed, sterilized container.

21. A kit as claimed in claim 18, 19 or 20 wherein said preselected radionuclide is an isotope of Tc.

22. A kit as claimed in claim 18, 19 or 20 wherein said preselected radionuclide is an isotope of Re.

23. A kit for converting a supply of .sup.99m Tc-pertechnetate to a complex as claimed in claim 1, said kit comprising a supply of an isonitrile and a supply of a reducing agent capable of reducing technetium.

24. A kit as claimed in claim 23 in which said reducing agent is selected from the class consisting of dithionites and stannous salts.

25. A kit as claimed in claim 23 wherein said isonitrile ligand and said reducing agent are lyophilized.

26. A kit as claimed in claim 23 wherein said lyophilized isonitrile ligand and reducing agent are contained in a sealed, sterilized container.

27. A kit as claimed in claim 18 wherein said radioactive metal is radioactive isotope of Tc, Ru, Co, Pt, Fe, Os or Ir.

28. A kit as claimed in claim 18 wherein said radioactive metal is a radioactive isotope of W, Re, Fe, or Os.

29. A kit as claimed in claim 18 wherein said isotope of Cr, Mo, Co, Tc, Fe, Mn, W, Ru, Ni, Rh, Ir, Pd, Nb or Ta.

30. A method for imaging body tissues comprising administering to an animal a radiopharmaceutical composition comprising a coordination complex of an isonitrile ligand and .sup.99m Tc, and detecting the localization of such complex in the body tissues by a gamma camera.

31. The method of claim 30 wherein said complex is .sup.99m Tc-hexakis-t-butylisonitrile.

32. The method of claim 30 wherein said complex is .sup.99m Tc-hexakis-iso-propylisonitrile.

33. A method for detecting vascular emboli in an animal comprising administering to said animal a radiopharmaceutical composition comprising a coordination complex of an isonitrile ligand and .sup.99m Tc, and detecting the emboli by localization of said complex at said emboli with a gamma camera.

34. The method of claim 33 wherein said complex is .sup.99m Tc-hexakis-t-butylisonitrile.

35. The method of claim 33 wherein said complex is .sup.99m Tc-hexakis-iso-propylisonitrile.

36. A method for labeling a cell or liposome comprising incubating said cell or liposome with a coordination complex as claimed in claim 1 in a suitable medium.
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