Radiolabeled compounds and liposomes and their method of making and using same

• US 7,718,160 B2
• Filed: 05/22/2003
• Issued: 05/18/2010
• Est. Priority Date: 07/02/2002
• Status: Active Grant

• Current Assignee: Nanotex, Corp.
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Goins, Beth, Phillips, William T., Bao, Ande
• Primary Examiner(s): Hartley; Michael G
• Assistant Examiner(s): SCHLIENTZ, LEAH H
• Application Number:
  US10/518,872
• Publication Number:
  US 20050222396A1
• Time in Patent Office: 2,553 Days
• Field of Search: 424/1.11, 424/1.21, 424/1.65, 424/1.61, 534/11, 534/14
• US Class Current: 424/1.65
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3
• CPC Class Codes: A61K 51/1234 Liposomes
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07F 13/005 Compounds without a metal-carbon linkage

Abstract

The invention, in one aspect, relates to radiolabeled compounds. The invention also relates to radiolabeled liposomes and methods of making and using thereof. The invention also relates to kits for preparing radiolabeled liposomes.

Claims

1. A compound having the formula I

2. The compound of claim 1, wherein R¹ is CH₂CH₂NEt₂ and R² is CH₂CH₂N(CH₂CH₂SH)(CH₂CH₂NEt₂).

3. The compound of claim 1, wherein R¹ is CH₂CH₂CH₂CH₃ and R² is CH₂CH₂N(CH₂CH₂SH)(CH₂CH₂CH₂CH₃).

4. A radiolabeled liposome comprising a liposome and a compound having the formula I

5. The radiolabeled liposome of claim 4, wherein the liposome further comprises a drug that is incorporated within the liposome.

6. The radiolabeled liposome of claim 5, wherein the drug is a compound comprising at least one thiol group.

7. The radiolabled liposome of claim 6, wherein the drug reacts with the compound having the formula I.

8. The radiolabeled liposome of claim 5, wherein the drug comprises glutathione, cysteine, N-acetyl cysteine, 2-mercaptosuccinic acid, 2,3-dimercaptosuccinic acid, captopril or a combination thereof.

9. The radiolabeled liposome of claim 4, wherein the liposome comprises a lipid.

10. The radiolabeled liposome of claim 4, wherein the liposome comprises a phospholipid.

11. The radiolabeled liposome of claim 4, wherein the liposome comprises a cholesterol or a cholesterol analogue.

12. The radiolabeled liposome of claim 10, wherein the liposome comprises distearoyl phosphatidyicholine.

13. The radiolabeled liposome of claim 4, wherein the amount of radionuclide attached or incorporated into the liposome is from about 0.01 mCi to about 400 mCi per 50 mg of lipid that is used to prepare the liposome.

14. The radiolabeled liposome of claim 4, wherein the liposome further comprises a chemotherapeutic agent, an antibiotic agent or a treatment molecule, wherein the chemotherapeutic agent, the antibiotic agent, or the treatment molecule is incorporated or attached to the liposome.

29. The radiolabeled liposome of claim 4, wherein R¹ is CH₂CH₂NEt₂ and R² is CH₂CH₂N(CH₂CH₂SH)(CH₂CH₂NEt₂).

15. A method of making a radiolabeled liposome, comprising mixing

a. a liposome having an outer space and an inner volume, wherein the pH of the inner volume of the liposome is less than the pH of the outer space of the liposome, with

b. a compound having the formula I

16. The method of claim 15, wherein the pH of the inner volume of the liposome is acidic and the pH of the outer space of the liposome is neutral, basic, or a physiological pH.

17. The method of claim 15, wherein the inner volume of the liposome contains a compound comprising at least one amine group or at least one carboxyl group.

18. The method of claim 15, wherein the inner volume of the liposome contains ammonium sulfate.

19. The method of claim 15, wherein the pH of the inner volume is from about 4 to about 7 and the pH of the outer space is from about 6 to about 7.4.

20. The method of claim 15, wherein after the liposome and the compound having the formula I are mixed, the radiolabeled liposome is incubated at from 25°

C. to 37°

C. for 0.5 to 2 hours.

21. The radiolabeled liposome produced by the method of claim 15.

30. The method of claim 15, wherein R¹ is CH₂CH₂NEt₂ and R² is CH₂CH₂N(CH₂CH₂SH)(CH₂CH₂NEt₂).

22. A method of making a radiolabeled liposome, comprising mixing

a. a liposome having an outer space and an inner volume, wherein a drug comprising at least one thiol group is incorporated within the inner volume of the liposome, with

b. a compound having the formula I

23. The method of claim 22, wherein the drug reacts with the compound having the formula I.

24. The method of claim 22, wherein the drug comprises glutathione, cysteine, N-acetyl cysteine, or a combination thereof.

25. The method of claim 22, wherein after the liposome and the compound having the formula I are mixed, the radiolabeled liposome is incubated at from 25°

C. to 37°

C. for 0.5 to 2 hours.

26. A radiolabeled liposome made by the method of claim 22.

31. The method of claim 22, wherein R¹ is CH₂CH₂NEt₂ and R² is CH₂CH₂N(CH₂CH₂SH)(CH₂CH₂NEt₂).

32. The method of claim 26, wherein R¹ is CH₂CH₂NEt₂ and R² is CH₂CH₂N(CH₂CH₂SH)(CH₂CH₂NEt₂).

27. A kit comprising

a. a liposome having an outer space and an inner volume, wherein the pH of the inner volume of the liposome is less than the pH of the outer space of the liposome, and

b. a compound having the formula I

33. The kit of claim 27, wherein R¹ is CH₂CH₂NEt₂ and R² is CH₂CH₂N(CH₂CH₂SH)(CH₂CH₂NEt₂).

28. A kit comprising

a. a liposome having an outer space and an inner volume, wherein a drug comprising at least one thiol group is incorporated within the inner volume of the liposome, and

b. a compound having the formula I

34. The kit of claim 28, wherein R¹ is CH₂CH₂NEt₂ and R² is CH₂CH₂N(CH₂CH₂SH)(CH₂CH₂NEt₂).