Positron emitter labeled enzyme inhibitors

Drug – bio-affecting and body treating compositions – Identification or warning feature – Taste or smell or chemical irritation to the eye – nose – or...

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424 9, 514651, 514654, 564353, 564381, 564382, A61K 4902, A61K 31135, C07C 9306, C07C 8728

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049138910

ABSTRACT:
This invention involves a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography.

REFERENCES:
Fowler, J. S., "Synthesis of .sup.14 C-Labeled Suicide Inactivators of MAO," J. Lab. Cmpds. and Radio., vol. 14, 3, 435-437, 1978.
Ishiwata et al., "Biodistribution of a Positron-Emitting Suicide Inactivator of MAO," J. Nucl. Med., 26, 630-636, 1985.
MacGregor et al., Biochemical Pharmacology, vol. 34, No. 17, pp. 3207-3210 (1985).
Inoue et al., J. Neurochemistry, vol. 44, No. 1, pp. 210-216 (1985).
Inoue et al., Japanese J. Nuclear Medicine, vol. 21, No. 6, pp. 671-678.

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