ENZYME TARGETED IMAGING AGENTS FOR NEUROPSYCHIATRY

$0P41FY2002RRNIH

University Of Wisconsin Madison, Madison WI

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Abstract

This project involves developing imaging agents which will allow the asessment of dopaminergic and serotonergic activity in the brain non-invasively using positron emission tomography (PET). Short-lived positron emitting isotopes, 18F (t+=110 min.) and 11C (t+=20 min.), are introduced into amino acid analogs which are substrates of the rate limiting enzymes in the biosynthesis of dopamine and serotonin. Non-radioactive samples of these compounds are first sythesized and characterized by multinuclear NMR (1H, 11C, 19F). In addition, both the precursors and enzyme products of the desired compounds are prepared and characterized by NMR. These precursors and enzyme products are used in the synthesis of the desired compounds and their metabolic characterization, respectively. Radiolabeled compounds are then evaluated, in vitro and in vivo, as imaging agents for use in the study of neuropsychiatric disorders such as Parkinson's disease, affective disorders and depression.

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