Compositions and methods for producing cellular labels for nuclear magnetic resonance techniques

• US 8,227,610 B2
• Filed: 07/10/2008
• Issued: 07/24/2012
• Est. Priority Date: 07/10/2007
• Status: Active Grant

• Current Assignee: Carnegie Mellon University
• Original Assignee: Carnegie Mellon University
• Inventors: Janjic, Jelena, Ahrens, Eric T.
• Primary Examiner(s): Andres, Janet
• Assistant Examiner(s): REESE, HEIDI L
• Application Number:
  US12/218,265
• Publication Number:
  US 20090074673A1
• Time in Patent Office: 1,475 Days
• Field of Search: None
• US Class Current: 546/79
• CPC Class Codes: A61K 49/126 Linear polymers, e.g. dextran, inulin, PEG
• CPC Class Codes: A61K 49/1806 Suspensions, emulsions, colloids, dispersions
• CPC Class Codes: A61K 49/1896 not provided for elsewhere, e.g. cells, viruses, ghosts, red blood cells, virus capsides
• CPC Class Codes: C08G 65/007 containing fluorine
• CPC Class Codes: C08L 2203/02 for biomedical use

Abstract

The disclosure provides, in part, compositions of perfluoro polyether compounds and associated methods for producing cellular labels for tracking cells by MRI and methods for labeling, detecting and quantifying cell numbers in vivo.

Claims

1. A compound of any one of formulae 1, 2, 6-7, or 10-15:

2. A composition comprising

a compound of formula 10 and a compound of formula 1, wherein each of said compounds is as defined in claim 1;

a compound of formula 12, which compound is as defined in claim 1 and a compound of formula 1;

compound of formula 14, which compound is as defined in claim 1 and a compound of formula 1;

a compound of formula 16;

3. A composition comprising

A) one or more compounds of claim 1 and a compound of formula 1a,

4. An emulsion comprising a compound of claim 1.

5. An emulsion selected from the group consisting of:

an emulsion comprising a compound of formula 1, which compound is as defined in claim 1, a compound of formula 16, which compound is as defined in claim 2, a compound of formula 17;

7. A method for preparing an emulsion of claim 4 or 5, comprising using low energy methods, wherein the low energy method optionally comprises a thin film method.

8. A method for preparing an emulsion of claim 4 or 5 comprising high energy methods, wherein the high energy method is optionally microfluidization or sonication.

9. A method for

I) labeling a cell, the method comprising contacting the cell ex vivo with a fluorocarbon imaging reagent comprising a compound of claim 1, under conditions such that the fluorocarbon imaging reagent becomes associated with the cell;

II) detecting a cell in a subject, the method comprising;

a) administering to the subject a cell that is labeled with a fluorocarbon imaging reagent comprising a compound of claim 1; and

b) examining at least a portion of the subject by a nuclear magnetic resonance technique, thereby detecting a labeled cell in the subject;

III) detecting transplanted cells in a transplant recipient, the method comprising;

a) administering cells for transplant to a transplant recipient, at least a portion of which cells for transplant are labeled with a fluorocarbon imaging reagent comprising a compound of claim 1; and

b) examining at least a portion of the subject by a nuclear magnetic resonance technique, thereby detecting the labeled cells;

IV) quantifying cell number in vivo, the method comprising;

a) administering to the subject cells that are labeled with a fluorocarbon imaging reagent comprising a compound of claim 1;

b) examining at least a portion of the subject by a nuclear magnetic resonance technique, thereby detecting labeled cells in the subject; and

c) quantifying the number of labeled cells in a region of interest (ROI);

V) labeling a cell, the method comprising contacting the cell in vivo with a fluorocarbon imaging reagent comprising a compound of claim 1, under conditions such that the fluorocarbon imaging reagent becomes associated with the cell;

or

VI) detecting a cell in a subject, the method comprising;

a) administering to the subject a fluorocarbon imaging reagent comprising a compound of claim 1; and

b) examining at least a portion of the subject by a nuclear magnetic resonance technique, thereby detecting a labeled cell in the subject.

10. A labeled cellular formulation for administration to a subject, the formulation comprising:

a) a cell; and

h) a fluorocarbon imaging reagent comprising a compound of claim 1, that is associated with the cell.

11. The compound of claim 1, wherein the compound is the compound of formula 1.

12. The compound of claim 1, wherein the compound is the compound of formula 2.

13. The compound of claim 1, wherein the compound is the compound of formula 6.

14. The compound of claim 1, wherein the compound is the compound of formula 7.

15. The compound of claim 1, wherein the compound is the compound of formula 10.

16. The compound of claim 1, wherein the compound is the compound of formula 11.

17. The compound of claim 1, wherein the compound is the compound of formula 12.

18. The compound of claim 1, wherein the compound is the compound of formula 13.

19. The compound of claim 1, wherein the compound is the compound of formula 14.

20. The compound of claim 1, wherein the compound is the compound of formula 15.

21. The composition of claim 2, wherein the composition comprises a compound of formula 16 and a compound of formula 1.

22. The composition of claim 2, wherein the composition comprises a compound of formula 40 and a compound of formula 1.

23. The composition of claim 2, wherein the composition comprises a compound of formula 12 and a compound of formula 29.

24. The emulsion of claim 5, wherein the emulsion comprises a compound of formula 1, a compound of formula 16, a compound of formula 17, a compound of formula 1a, a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) tri-block copolymer with an average molecular weight of 8400, an average number of PEO units of about 153, and an average number of PPO units of about 29, and prolamine sulfate.

25. The emulsion of claim 5, wherein the emulsion comprises a compound of formula 1, a compound of formula 16, a compound of formula 17, a compound of formula 1a, a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) tri-block copolymer with an average molecular weight of 8400, an average number of PEO units of about 153, and an average number of PPO units of about 29, and polyethylamine.

26. The emulsion of claim 5, wherein the emulsion comprises a compound of formula 1, a compound of formula 40, a compound of formula 41, a compound of formula 1a, a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) tri-block copolymer with an average molecular weight of 8400, an average number of PEO units of about 153, and an average number of PPO units of about 29, and prolamine sulfate.

27. The emulsion of claim 5, wherein the emulsion comprises a compound of formula 1, a compound of formula 40, a compound of formula 41, a compound of formula 1a, a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) tri-block copolymer with an average molecular weight of 8400, an average number of PEO units of about 153, and an average number of PPO units of about 29, and polyethylamine.

28. The emulsion of claim 5, wherein the emulsion comprises a compound of formula 1a, a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) tri-block copolymer with an average molecular weight of 8400, an average number of PEO units of about 153, and an average number of PPO units of about 29, and polyethylamine.

29. An emulsion comprising a composition of claim 2.

30. An emulsion comprising a composition of claim 3.

6. A method for preparing a composition comprising a compound of formula 1 and a compound of formula 38: