The purpose of this work is to develop procedures with monkeys for quantification of dopamine receptor occupancy and dopamine release using PET and 11C-raclopride. Seven studies have been performed to date. Initial studies have used bolus injections of tracer, followed by serial PET scanning and blood sampling with metabolite determinations by HPLC. These data permit the quantification of the tissue volume of distribution (VD), a measure of total tissue binding (free, nonspecifically bound, and specifically bound tracer). Comparison of the measured VD values between control states and following administration of amphetamine (which produces pre-synaptic release of dopamine) demonstrated 30-50% reduction in raclopride binding. The next phase of study involves development of an infusion protocol to produce true equilibrium to allow measurement of the time course of raclopride displacement following amphetamine. Subsequently, PET studies will be combined with in vivo microdialysis for measurement of dopamine and raclopride levels. The combination of dopamine time course information from microdialysis and the PET dynamic data may allow exact quantification of the magnitude of dopamine release.
