Our first study indicated that serotonin synthesis rates determined by the use of alpha-methyltryptophan (MTP) and PET imaging were found to be highly correlated to free plasma tryptophan concentrations, a parameter that is not well correlated to the regulation of serotonin synthesis rates under steady state conditions, and not to cerebrospinal fluid concentrations of 5-hydroxy-indole-3-acetic acid, long considered a measure of central serotonin turnover.(Neuropsychopharmacology 19(5):345-353, 1998). In order to determine what is actually being measured by alpha-MTP uptake, 11-C and 14-C labeled compoundwere co- administered to four rhesus monkeys. After a one hour PET scan, animals were euthanized and brain tissues were taken and frozen at -80 degrees C. HPLCanalysis with flourometric detection and fraction collection indicates that alpha-MTPis minimally converted to alpha- methylserotonin; there is less than 4% conversionin the dorsal raphe nucleus and less than 0.6% in cortical regions. We conclude that alpha- MTP is acting primarily as a tracer of tryptophan uptake in the 1 hour followingintravenous infusion and is unsuitable for measuring serotonin synthesis rate using PositronEmission Tomography (paper in press to Journal of Cerebral Blood Flow and Metabolism).Development of ligands for detection of serotonin receptors continues. A study is currently being performed with [11-C]MDL-100907. A protocol is being written for use of a fluorine derivative of WAY-100635. - serotonin, Brain, rhesus monkey, alpha-methyl-tryptophan, antagonists, 5HT1A, 5HT2A, PET
