PET RADIOTRACERS FOR IMAGING FATTY ACID METABOLISM AND STORAGE

• US 20120100073A1
• Filed: 05/04/2010
• Published: 04/26/2012
• Est. Priority Date: 05/04/2009
• Status: Abandoned Application

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Mach, Robert H., Tu, Zhude, Gropler, Robert John, Herrero, Pilar
• Application Number:
  US13/319,001
• Publication Number:
  US 20120100073A1
• Time in Patent Office: Days
• US Class Current: 424/1.89
• CPC Class Codes: A61K 51/0402 carboxylic acid carriers, fatty acids amino acids A61K51/0406
• CPC Class Codes: C07B 59/00 Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
• CPC Class Codes: C07C 51/09 from carboxylic acid esters or lactones
• CPC Class Codes: C07C 59/64 containing six-membered aromatic rings
• CPC Class Codes: C07C 59/68 the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
• CPC Class Codes: C07D 249/04 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles

Abstract

Fatty acid analogue (FAA) molecules comprising positron-emitting radionuclides, salts thereof, and FAA-triglycerides are disclosed. Also disclosed are methods of synthesis, and methods of imaging distribution and metabolism of fatty acids and fatty acid triglycerides.

Claims

1. A fatty acid analog or salt thereof of structure

2. A fatty acid analog or salt thereof in accordance with claim 1, wherein the fatty acid analog is

3. A fatty acid analog or salt thereof in accordance with claim 2, wherein X is a fluorine.

6. A fatty acid analog or salt thereof in accordance with claim 2, wherein X is an ¹⁸F.

7. A fatty acid analog or salt thereof in accordance with claim 2, wherein m=2.

8. A fatty acid analog or salt thereof in accordance with claim 2, wherein n=14.

9. A fatty acid analog or salt thereof in accordance with claim 1, wherein n=14, m=2 and X is ¹⁸F.

4-5. -5. (canceled)

10-20. -20. (canceled)

21. An ¹⁸F-fatty acid analog-very low density lipoprotein triglyceride (¹⁸F-FAA-VLDL) of structure

22. An ¹⁸F-FAA-VLDL or salt thereof in accordance with claim 21, wherein n=14.

23-30. -30. (canceled)

31. A method of synthesizing

32. A method in accordance with claim 31, wherein n=14.

33. A method in accordance with claim 31, further comprising:

a) contacting Br—

(CH₂)_n—

COOH 1 with trimethylsilyl diazomethane and THF to yield Br—

(CH₂)_n—

COOCH₃ 2;

b) contacting the Br—

(CH₂)_n—

COOCH₃ 2 with 4-benzyloxyphenylboronic acid, Pd(OAc)₂, [Hp(t-Bu)₂Me]BF₄, KOt-Bu and t-amyl alcohol to yield

34-45. -45. (canceled)

46. A method of synthesizing

47. A method in accordance with claim 46, wherein n=14.

48-51. -51. (canceled)

52. A method of determining fatty acid distribution in an mammal, comprising:

administering to the mammal a radiolabeled fatty acid analog or salt thereof

54. A method in accordance with claim 52, wherein n=14.

55. A method in accordance with claim 52, further comprising subjecting image data to analysis by an algorithm in a digital computer.

56. A method in accordance claim 52, further comprising displaying the fatty acid distribution in an image on a computer display.

53. (canceled)

57. A method of imaging distribution of fatty acid triglycerides in a mammal, comprising:

administering to the mammal a radiolabeled fatty acid triglyceride analog or salt thereof

58. A method in accordance claim 57, wherein n=14.

59. A method in accordance claim 57, further comprising:

subjecting image data to analysis by an algorithm in a digital computer.

60. A method in accordance with claim 57, further comprising displaying fatty acid triglyceride distribution on a computer display.