# US 8,273,326 B2 · Imaging infection with compounds that bind to thymidine kinase

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- Number: US 8,273,326 B2
- Document ID: US8273326B2
- Status: Granted
- Kind: B2
- Application number: 11/629,607
- Filed: 2005-06-20
- Published: 2009-01-08
- Granted: 2012-09-25
- Earliest claimed: 2004-06-18
- Assignees: The Johns Hopkins University
- Inventors: Martin G. Pomper; Chetan Bettegowda; Catherine Foss; Shibin Zhou; Kenneth Kinzler; Bert Vogelstein
- Web page: https://patentgrep.com/patent/US8273326B2

## CPC

- A61K 51/1241: {particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins}
- A61K 51/0491: {Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers}
- A61K 51/1231: {Aerosols or breath tests, e.g. administration of gasses, emanators}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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

### Claim 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.

### Claim 2 (depends on 1)

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).

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 3)

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).

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

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.

### Claim 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.

### Claim 9 (depends on 8)

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).

### Claim 10 (depends on 8)

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).

### Claim 11 (depends on 8)

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

### Claim 12 (depends on 8)

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

### Claim 13 (depends on 8)

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

### Claim 14 (depends on 8)

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

### Claim 15 (depends on 14)

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

### Claim 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.

### Claim 17 (depends on 16)

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).

### Claim 18 (depends on 16)

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

### Claim 19 (depends on 18)

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).

### Claim 20 (depends on 16)

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

### Claim 21 (depends on 16)

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