Positron emission tomography probe to monitor selected sugar metabolism in vivo
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.
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.