Labelled carboxylic acids and their uses in molecular imaging

Patent metadata

Field	Value
Publication number	US-10213516-B2
Application number	US-201414889558-A
Country	US
Kind code	B2
Filing date	May 8, 2014
Priority date	May 8, 2013
Publication date	Feb 26, 2019
Grant date	Feb 26, 2019

Abstract

The present invention pertains generally to the field of imaging compounds, and more specifically to certain 2,2-dialkyl radionuclide-labelled carboxylic acids suitable for PEWT, SPECT and/or DNP imaging. Also described are uses of such compounds in the imaging of, inter alia, cancer tumors, metastasis, Alzheimer's disease and multiple sclerosis.

First claim

The invention claimed is:

1. A composition comprising a tracer, wherein the tracer is a radionuclide-labelled 2,2-di-C 1-4 -alkylpropanoic acid, 2,2-di-C 1-4 -alkylbutanoic acid, 2,2-di-C 1-4 -alkylpentanoic acid, or the corresponding carboxylate, wherein the radionuclide-labelled carboxylic acid is a compound of formula (I):

Wherein
Q is a suitable radionuclide;
C L is selected from [ 11 C]carbon, [ 12 C]carbon, or [ 13 C]carbon;
n is 1, 2, or 3;
R 1 and R 2 are independently C 1-4 -alkyl; and
R 3 and R 4 are independently H or F.

2. The composition of claim 1 , wherein R 3 and R 4 are both hydrogen.

3. The composition of claim 1 , wherein n is 1 or 2, optionally wherein n is 1.

4. The composition of claim 1 , wherein R 1 and R 2 are both methyl.

5. The composition of claim 1 , wherein the radionuclide Q is selected from [ 11 C]carbon, [ 18 F]fluorine, [ 13 N]nitrogen, [ 15 O]oxygen, [ 76 Br]bromine, [ 123 I]iodine, [ 124 I]iodine, and [ 125 I]iodine.

6. The composition of claim 1 , wherein the radionuclide is [ 18 F]fluorine.

7. The composition of claim 1 , wherein C L is [ 12 C]carbon.

8. The composition of claim 1 , wherein the carboxylic acid is [1- 12 C][ 18 F]3-fluoro-2,2-dimethylpropanoic acid.

9. The composition of claim 1 , wherein the carboxylic acid is [1- 13 C][ 18 F]3-fluoro-2,2-dimethylpropanoic acid.

10. The composition of claim 1 , wherein the carboxylic acid is [1- 13 C]3-fluoro-2,2-dimethylpropanoic acid.

11. A method of imaging for diagnosing a condition in a subject, wherein the method comprises:
(i) administering the composition of claim 1 to the subject;
(ii) detecting gamma rays emitted, either directly or indirectly, by the tracer;
(iii) acquiring at least one image associated with the gamma rays emitted by the tracer; and
(iv) diagnosing the condition in the subject using the image.

12. A method of imaging for diagnosing a condition in a subject, wherein the subject has been pre-administered a composition according to claim 1 , wherein the method comprises:
(i) detecting gamma rays emitted, either directly or indirectly, by the tracer;
(ii) acquiring at least one image associated with the gamma rays emitted by the tracer; and
(iii) diagnosing the condition in the subject using the image.

13. The method of diagnosis of claim 11 , wherein the method of imaging is positron emission tomography (PET).

14. The method of diagnosis of claim 11 , wherein the method of imaging is single-photon emission computed tomography (SPECT).

15. The method of diagnosis of claim 12 , wherein a second imaging technique is used.

16. The method of diagnosis of claim 12 , wherein the condition is a lesion or diseased tissue that has an altered lipid turnover compared to levels in healthy tissue of the same organ or origin.

17. The method of diagnosis of claim 12 , wherein the condition is a tumour.

18. The method of diagnosis of claim 17 , wherein the tumour is a cancer tumour.

19. The method of diagnosis of claim 18 , wherein the cancer is breast, brain, prostate, colon, esophageal, lung, pancreatic or liver cancer.

20. The method of diagnosis of claim 18 , wherein the cancer is breast, brain, or prostate cancer.

21. The method of diagnosis of claim 12 , wherein the tumour is a hypoxic tumour.

22. The method of diagnosis of claim 12 , wherein the tumour has perturbed carnitine metabolism.

23. The method of diagnosis of claim 12 , wherein the condition is metastasis.

24. The method of diagnosis of claim 12 , wherein the condition is Alzheimer's disease.

25. The method of diagnosis of claim 12 , wherein the condition is multiple sclerosis.

26. The method of diagnosis of claim 12 , wherein the condition is a heart-related disease or disorder.

27. The method of diagnosis of claim 12 , wherein the condition is a genetic/epigenetic disease of lipid metabolism.

28. The method of claim 12 , wherein the method further comprises the step of comparing the image with a previously obtained image to monitor progression of the condition and/or response to therapy.

Assignees

• Imperial Innovations Ltd

Inventors

• Aboagye Eric O
• Iddon Lisa
• Pisaneschi Federica
• Witney Timothy H

Classifications

• C07C53/21

  containing fluorine · CPC title

• C07C51/09

  from carboxylic acid esters or lactones · CPC title

• A61K51/0402 Primary

  carboxylic acid carriers, fatty acids (amino acids A61K51/0406) · CPC title

• C07B59/001

  Acyclic or carbocyclic compounds · CPC title