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 pre-clinical toxicology in rabbits and mice has been completed. The dosimitry studies in Rhesus macaques to measure individual organ exposure to CMAT have also been completed and sent to Oak Ridge for calculation of individual organ exposure. Once this is completed an IND will be submitted to the FDA for use of CAMT in humans as a PET ligand. The synthesis of L-CAMT is now running well and sufficient quantities of L-CAMT can be produced. Preliminary to using L-CAMT in humans we have been performing L-CAMT PET scans on rhesus monkeys. These monkeys are animals whose social behavior has been observed and rated since birth. In addition, multiple CSF samples have been analyzed for serotonin metabolites (5-HIAA) in all these animals. Thus far three low CSF 5-HIAA and three high CSF 5-HIAA monkeys have been scanned. This study will demonstrate how accurately the accummulation of L-CAMT as measured by PET reflects the turnover of serotonin as indexed by CSF 5-HIAA. We expect to begin human studies by the end of 1996.
