Hyperpolarized and deuterium exchanged hyperpolarized13c and 15n-labeled xanthine, arginine, glutamine, and urea probes
AssigneeMemorial Sloan Kettering Cancer Center
InventorsAndrew CHO, Roozbeh ESKANDARI, Valentina D. GIALLEONARDO, Kayvan R. KESHARI
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Abstract
The present technology provides 13C- and 15N-labeled probes for imaging one or more mammalian cells using magnetic resonance. Thus, 13C- and 15N-labeled arginine (compound of formula I), xanthine (compounds of formula II and formula III), urea (compounds of formula IV), and glutamine (compounds of formula V), stereoisomers, tautomers, and pharmaceutically acceptable salts thereof are provided. Further methods of making the labelled probes and methods of using the probes to detect arginase, xanthine oxidase, and glutaminase metabolites and activity are provided.
Claims22
A compound according to formulae I, II, or III:
- stereoisomers, tautomers, and/or pharmaceutically acceptable salts thereof;
- wherein:
- L1 is 15N;
- L2 is 13C;
- and
- is a member selected from the group consisting of , , and a mixture thereof.
3-4. (canceled)
6-13. (canceled)
A method of imaging comprising:
- administering an effective amount of a composition comprising a hyperpolarized probe to one or more mammalian cells;
- detecting by magnetic resonance the hyperpolarized probe and/or a metabolite of the probe in the one or more mammalian cells;
- wherein the hyperpolarized probe is a compound that has been subjected to hyper polarization and is selected from the group consisting of a compound according to formulae I, II, or III:
- stereoisomers, tautomers, and/or pharmaceutically acceptable salts thereof;
- wherein:
- L1 is 15N;
- L2 is 13C;
- and
- is a member selected from the group consisting of , , and a mixture thereof.
The method of claim 4 wherein the hyperpolarized probe is hyperpolarized compound of formula I, a stereoisomer thereof, and/or a tautomer thereof, and/or a pharmaceutically acceptable salt thereof, and the metabolite is produced by arginase.
A method of imaging comprising:
- contacting one or more mammalian cells with an effective amount of a composition comprising a deuterium exchanged-hyperpolarized probe;
- and
- detecting by magnetic resonance the deuterium exchanged-hyperpolarized probe and/or a metabolite of the probe in the one or more mammalian cells;
- wherein the deuterium exchanged-hyperpolarized probe is a deuterated compound of formula I, stereoisomers, tautomers, and/or pharmaceutically acceptable salts thereof, a deuterated compound of formula IV
- and/or tautomers thereof, or
- a deuterated compound of formula V
- stereoisomers, tautomers, and/or pharmaceutically acceptable salts thereof;
- and
- the deuterated compound has been subjected to hyper polarization.
A deuterium exchanged-hyperpolarized probe comprising a compound of formula VI
- or
- formula VII
- stereoisomers, tautomers, and/or pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.