IP Library Granted Patent US 8,273,326
Granted Patent B2
US 8,273,326 · App. 11/629,607 · Granted Sep 25, 2012

Imaging infection with compounds that bind to thymidine kinase

Assignee: The Johns Hopkins University
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Quick Facts
Patent No.
US 8,273,326
App. No.
11/629,607
Granted
Sep 25, 2012
Kind
B2
Abstract

The instant invention provides a method for diagnosing an infection in a subject by administering to the subject a compound suitable for imaging which binds to a thymidine kinase present in the infecting organism, and obtaining an image of the subject to determine the presence and location of the compound, wherein a localization of the compound is indicative that the subject has an infection.

Claims (29)

1. A method for diagnosing a bacterial infection in a subject comprising:

administering to the subject a compound suitable for imaging which binds to an endogenous bacterial thymidine kinase present in the infecting bacteria; and

obtaining an image of the subject to determine the presence and location of the compound; wherein a localization of the compound is indicative that the subject has a bacterial infection wherein the compound is a radiolabeled nucleoside.

2. The method of claim 1 , wherein the image of the subject is acquired by a method selected from the group consisting of planar gamma imaging, single photon emission computed tomography (SPECT) and positron emission tomography (PET).

3. The method of claim 1 , wherein the nucleoside analog is labeled with radioactive fluorine or iodine.

4. The method of claim 3 , wherein the compound is selected from the group consisting of 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([125I]-FIAU), 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([124I]-FIAU), 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]-FHBG), (18)F-1-(2′-deoxy-2′-fluoro-beta-d-arabinofuranosyl)thymine ([18F]-FMAU), 18F-2′-fluoro-2′deoxy-1beta-D-arabinofuranosyl-5-ethyl-uracil ([18F]-FEAU) and 1-(2′-deoxy-2′-fluoro-beta-D-arabinofuranosyl)-5-[18F] iodouracil ([18F]-FIAU).

5. The method of claim 1 , wherein the nucleoside analog emits gamma particles.

6. The method of claim 1 , wherein the nucleoside analog is fluorescent.

7. The method of claim 1 , wherein the bacterial infection is caused by bacteria from a genus selected from the group consisting of Escherichia, Bacillus, Chromobacterium, Clostridium, Enteroccus, Haemophilus, Listeria, Mycoplasma, Pasteruella, Salmonella, Staphylococcus, Streptococcus, Streptomyces, Vibrio , and Yersinia.

8. A method for imaging a bacterial infection in a subject comprising:

administering to the subject a compound suitable for imaging which binds to an endogenous bacterial thymidine kinase present in the infecting bacteria; and

obtaining an image of the subject;

thereby obtaining an image of the bacterial infection in a subject wherein the compound is a radiolabeled nucleoside.

9. The method of claim 8 , wherein the image of the subject is acquired by a method selected from the group consisting of planar gamma imaging, single photon emission computed tomography (SPECT) and positron emission tomography (PET).

10. The method of claim 8 , wherein the compound is selected from the group consisting of 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([125I]-FIAU), 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([124I]-FIAU), 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]-FHBG), (18)F-1-(2′-deoxy-2′-fluoro-beta-d-arabinofuranosyl)thymine ([18F]-FMAU), 18F-2′-fluoro-2′deoxy-1beta-D-arabinofuranosyl-5-ethyl-uracil ([18F]-FEAU) and 1-(2′-deoxy-2′-fluoro-beta-D-arabinofuranosyl)-5-[18F] iodouracil ([18F]-FIAU).

11. The method of claim 8 , wherein the nucleoside analog emits gamma particles.

12. The method of claim 8 , wherein the nucleoside analog is fluorescent.

13. The method of claim 8 , wherein the compound suitable for imaging is an antibacterial compound.

14. The method of claim 8 , where the method allows for the differentiation of bacterial infection and inflammation.

15. The method of claim 14 , wherein the compound is an antibacterial, antiviral, or antifungal compound.

16. A method for imaging bacterial-based anticancer therapy comprising:

administering to a subject a compound suitable for imaging which binds to an endogenous bacterial thymidine kinase present in a therapeutic bacteria; and

imaging the subject to determine the presence and location of the compound;

thereby imaging a bacterial-based anticancer therapy wherein the compound is a radiolabeled nucleoside.

17. The method of claim 16 , wherein the image of the subject is acquired by a method selected from the group consisting of planar gamma imaging, single photon emission computed tomography (SPECT) and positron emission tomography (PET).

18. The method of claim 16 , wherein the nucleoside analog is labeled with radioactive fluorine or iodine.

19. The method of claim 18 , wherein the compound is selected from the group consisting of 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([125I]-FIAU), 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([124I]-FIAU), 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]-FHBG), (18)F-1-(2′-deoxy-2′-fluoro-beta-d-arabinofuranosyl)thymine ([18F]-FMAU), 18F-2′-fluoro-2′deoxy-1beta-D-arabinofuranosyl-5-ethyl-uracil ([18F]-FEAU) and 1-(2′-deoxy-2′-fluoro-beta-D-arabinofuranosyl)-5-[18F] iodouracil ([18F]-FIAU).

20. The method of claim 16 , wherein the nucleoside analog emits gamma particles.

21. The method of claim 16 , wherein the nucleoside analog is fluorescent.

Assignments (2)
CONFIRMATORY LICENSE Recorded Oct 26, 2017
From: JOHNS HOPKINS UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 044294/0456 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 17, 2011
From: POMPER, MARTIN G.; BETTEGOWDA, CHETAN; FOSS, CATHERINE; ZHOU, SHIBIN; KINZLER, KENNETH; VOGELSTEIN, BERT
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 027247/0330 →
Continuity (2)
Provisional Application 60581222 · Jun 18, 2004
Related Publication 20090010844A1 · Jan 8, 2009