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 dosimetry studies in Rhesus macaques to measure individual organ exposure to CMAT have also been completed. 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 12 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. The results of these studies show that use of the L-CAMT method for determining serotonin synthesis rates has several serious methodological and theoretical shortcomings which preclude the use of this method in humans; for this reason this project is being terminated. See report Z01 AA 00098-01 LCS for details.
