This project is designed to develop and implement a novel positron emitting tracer 11-C-alpha-methyl-tryptophan (CAMT) in order to measure the local distribution and accumulation of brain serotonin in patients with alcoholism, varying degrees of aggressive/impulsive behavior, and normal volunteers. CAMT is currently not approved for human use in the United States. In order to develop CAMT for humans, we must provide toxicology and dosimetry data that fulfill Food and Drug Administration (FDA) and Radiation Safety Committee guidelines, gather kinetic data in higher animals, and modify the synthesis to produce the L-form of CAMT. The Request for Proposal (RFP) will be released in the Commerce Business Daily in early fall. The RFP calls for completion of the project within four months after award of contract. This will give toxicology information necessary for FDA approval of alpha-methyl-tryptophan in humans. Concomitantly, Dr. Schmall will synthesize CAMT to measure organ dosimetry in Rhesus monkeys. After these data are acquired, application for use of CAMT in humans will be submitted to the FDA. Dr. Shoaf is determining pharmacokinetic, distribution, and enzyme kinetic properties in Rhesus monkeys so that these data may be used to calculate values for serotonin synthesis in both monkeys and humans.
