Positron emission tomography probe to monitor selected sugar metabolism in vivo

Patent metadata

Field	Value
Publication number	US-9592309-B2
Application number	US-201314399701-A
Country	US
Kind code	B2
Filing date	May 9, 2013
Priority date	May 9, 2012
Publication date	Mar 14, 2017
Grant date	Mar 14, 2017

Abstract

The invention disclosed herein discloses selected ribose isomers that are useful as PET probes (e.g. [18F]-2-fluoro-2-deoxy-arabinose). These PET probes are useful, for example, in methods designed to monitor physiological processes including ribose metabolism and/or to selectively observe certain tissue/organs in vivo. The invention disclosed herein further provides methods for making and using such probes.

First claim

The invention claimed is:

1. A method of observing cellular metabolism in vivo in a mammal, the method comprising the steps of:
(a) administering a composition to the mammal comprising a positron emission tomography (PET) probe selected from the group consisting of 18 F labelled:
2-fluoro-2-deoxyarabinose;
3-fluoro-3-deoxyarabinose;
2-fluoro-2-deoxyribose;
3-fluoro-3-deoxyribose;
1-fluoro-1-deoxy-alpha-ribose; and
1-fluoro-1-deoxy-beta-ribose;

(b) allowing the probe to accumulate in cells in the mammal; and
(c) observing the accumulated probe in the mammal using a positron emission tomography and a computed tomography (CT) process;
so that cellular metabolism in the mammal is observed.

2. The method of claim 1 , wherein the cellular metabolism that is observed in vivo comprises a metabolic profile observed in a pathological condition.

3. The method of claim 1 , wherein the cellular metabolism that is observed in vivo comprises a metabolic profile observed in response to a therapeutic agent administered to the mammal.

4. The method of claim 1 , wherein the mammal that is monitored has been administered an oxythiamine, an insulin, an metformin, a leflunomide or a methotrexate composition.

5. The method of claim 1 , wherein:
the mammal is a human;
the PET probe consists of:

 (2-fluoro-2-deoxyarabinose); and
cellular metabolism in liver, kidney, and/or intestinal tissues is selectively observed using a positron emission tomography process.

6. The method of claim 1 , wherein probe that accumulates in the cells is phosphorylated by a ribokinase expressed by the cells.

7. A method of selectively observing a tissue or organ in vivo in a mammal, the method comprising the steps of:
(a) administering a composition to the mammal comprising a positron emission tomography (PET) probe selected from the group consisting of ‘ 8 F labelled:
2-fluoro-2-deoxyarabinose;
3-fluoro-3-deoxyarabinose;
2-fluoro-2-deoxyribose;
3-fluoro-3-deoxyribose;
1-fluoro-1-deoxy-alpha-ribose; or
1-fluoro-1-deoxy-beta-ribose;

(b) allowing the probe to selectively accumulate in the tissue or organ; and
(c) observing the accumulated probe in the mammal using a positron emission tomography and a computed tomography process;
so that the tissue or organ is selectively observed in vivo in the mammal.

8. The method of claim 7 , wherein the positron emission tomography probe is administered to the mammal in combination with a pharmaceutically acceptable compound comprising a diluent, a carrier, or a binding agent.

9. The method of claim 7 , wherein the method observes cellular metabolism in liver, kidney, and/or intestinal tissues.

10. The method of claim 9 , wherein the observed cellular metabolism is metabolism observed in at least one of:
a metabolic disorder;
tumor growth;
gluconeogenesis;
de novo nucleotide synthesis
a neurodegenerative syndrome;
a syndrome characterized by ischemia;
a syndrome characterized by chronic inflammation;
congestive heart failure; or
stroke.

11. The method of claim 7 , wherein the method observes a physiological activity in the tissue or organ that is observed in at least one of: tissue dysfunction; tissue regeneration; or tissue neoplasm.

12. The method of claim 1 or claim 7 , wherein the positron emission tomography (PET) probe is 18 F labelled 2-fluoro-2-deoxyarabinose.

13. The method of claim 7 , wherein the positron emission tomography (PET) probe is 18 F labelled 3-fluoro-3-deoxyarabinose.

14. The method of claim 1 or claim 7 , wherein the positron emission tomography (PET) probe is 18 F labelled 2-fluoro-2-deoxyribose.

15. The method of claim 1 or claim 7 , wherein the positron emission tomography (PET) probe is 18 F labelled 3-fluoro-3-deoxyribose.

16. The method of claim 1 or claim 7 , wherein the positron emission tomography (PET) probe is 18 F labelled 1-fluoro-1-deoxy-alpha-ribose.

17. The method of claim 1 or claim 7 , wherein the positron emission tomography (PET) probe is 18 F labelled 1-fluoro-1-deoxy-beta-ribose.

Assignees

• Univ California

Inventors

• Witte Owen
• Clark Peter M
• Castillo Blanca Graciela Flores
• Jung Michael E
• Evdokimov Nikolai M

Classifications

• A61B6/032

  Transmission computed tomography [CT] · CPC title

• C07H5/02

  to halogen · CPC title

• A61K49/0433

  containing an organic halogenated X-ray contrast-enhancing agent · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• A61K51/0491 Primary

  Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers · CPC title