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Details for Patent: 5,976,496

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Details for Patent: 5,976,496

Title: Labeled somatostatin analogs for imaging cardiovascular disease
Abstract:The present invention provides methods and kits for detecting cardiovascular disease in a living mammal, using a labeled form of a somatostatin analog. The methods and kits of the invention provide early detection of atherosclerotic plaque, in particular, unstable atherosclerotic plaque, thus allowing therapeutic intervention prior to acute and potentially fatal incidents of cardiovascular disease.
Inventor(s): Dean; Richard T. (Bedford, NH), Lister-James; John (Bedford, NH)
Assignee: Diatide, Inc. (Londonderry, NH)
Filing Date:Nov 24, 1997
Application Number:08/976,995
Claims:1. A method of imaging a lesion in a cardiovascular system of a living mammal, comprising the steps of:

a) administering to the mammal a diagnostically effective amount of a labeled somatostatin analog;

b) exposing the mammal to an imaging apparatus capable of detecting the analog; and

c) detecting accumulation of the analog in the cardiovascular system.

2. The method of claim 1, wherein the analog is selected from the group consisting of a linear somatostatin analog and a cyclic somatostatin analog.

3. The method of claim 2, wherein the analog is a cyclic somatostatin analog.

4. The method of claim 3, wherein the analog is selected from the group

cycle.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.delta.-Orn)GCK.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.beta.-Dap)KCK.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.CGC;

cyclo.(N--CH.sub.3)F.YW.sub.3 KV.Hcy(CH.sub.2 CO.(.epsilon.-K)GC.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.GGC.amide);

cyclo(N--CH.sub.3)FFW.sub.D KTFCC.sub.Acm GC.sub.Acm amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 COGGCK.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 CO(.epsilon.-K)GCK.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 COGGCR.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 CO(.epsilon.-K)KC.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 COGGC.Orn.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 CO(.beta.-Dap)KC.amide);

cyclo.(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 CO.KKKKK(.epsilon.-K)GC.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.GGCKK.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.K(.epsilon.-K)GC.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.C.sub.Acm GC.sub.Acm.amide); and

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.CGCE.amide).

5. The method of claim 4, wherein the analog is

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.delta.-Orn)GCK.amide).

6. The method of claim 1, wherein the analog is labeled with a radioactive label, a fluorescent label, a paramagnetic label, a detectable heavy element or a detectable rare earth ion.

7. The method of claim 6, wherein the label is a radioactive label.

8. The method of claim 7, wherein the label is selected from the group consisting of .sup.123 I, .sup.67 Ga, .sup.111 In, and .sup.99m Tc.

9. The method of claim 8, wherein the label is .sup.99m Tc.

10. The method of claim 9, wherein the analog is

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.delta.-Orn)GCK.amide).

11. A kit for imaging a cardiovascular lesion comprising:

a) a sealed vial containing a predetermined quantity of a labeled or unlabeled form of a somatostatin analog; and

b) written instructions for accomplishing cardiovascular imaging using a labeled form of the analog.

12. The kit of claim 11, wherein the analog is selected from the group consisting of a linear somatostatin analog and a cyclic somatostatin analog.

13. The kit of claim 12, wherein the analog is a cyclic somatostatin analog.

14. The kit of claim 13, wherein the analog is selected from the group consisting of:

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.delta.-Orn)GCK.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.delta.-Dap)KCK.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.CGC.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.GGC);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.epsilon.-K)GC.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.GGC.amide);

cyclo(N--CH.sub.3)FFW.sub.D KTFCC.sub.Acm GC.sub.Adm. amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 COGGCK.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 CO(.epsilon.-K)GCK.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 COGGCR.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 CO(.epsilon.-K)KC.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 COGGC.Orn.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 CO(.beta.-Dap)KC.amide);

cyclo(N--CH.sub.3)FYW.sub.D KV.Hcy(CH.sub.2 CO.KKKKK(.epsilon.-K)GC.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.GGCKK.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.K(.epsilon.-K)GC.amide);

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.C.sub.Acm GC.sub.Acm.amide); and

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.CGCE.amide).

15. The kit of claim 14, wherein the analog is

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.delta.-Orn)GCK.amide).

16. The kit of claim 11, wherein the analog is labeled with a radioactive label, a fluorescent label, a paramagnetic label, a detectable heavy element or detectable rare earth ion.

17. The kit of claim 16, wherein the label is a radioactive label.

18. The kit of claim 17, wherein the label is selected from the group consisting of .sup.123 I, .sup.67 Ga, .sup.111 In, and .sup.99m Tc.

19. The kit of claim 18, wherein the label is .sup.99m Tc.

20. The kit of claim 19, further comprising a reducing agent.

21. The kit of claim 20, wherein the reducing agent is selected from the group consisting of a stannous ion containing agent, a dithionite ion containing agent, and a ferrous ion containing agent.

22. The kit of claim 19, wherein the analog is

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.delta.-Orn)GCK.amide) and the label is .sup.99m Tc.

23. The kit of claim 11, wherein the sealed vial contains an unlabeled from of the analog.

24. The kit of claim 23, further comprising a reducing agent.

25. The kit of claim 24, wherein the reducing agent is selected from the group consisting of a stannous ion containing agent, a dithionite ion containing agent, and a ferrous ion containing agent.

26. The kit of claim 23, wherein the analog is

cyclo.(N--CH.sub.3)F.YW.sub.D KV.Hcy(CH.sub.2 CO.(.delta.-Orn)GCK.amide).
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