PET scanning--a new tool in clinical psychopharmacology

Quantitative methods were developed for the determination of dopamine and benzodiazepine receptor characteristics in the living human brain by positron emission tomography (PET). As ligands, the 11C-labelled analogues of the selective antagonists of dopamine receptor subtypes, SCH 23390 and raclopride, and the benzodiazepine antagonist, Ro 15-1788, were used. Tracer amounts of the ligands were injected intravenously into healthy volunteers and schizophrenic patients. The distribution of ligand indicated high densities of D1 as well as D2 dopamine receptors in the basal ganglia. Binding of [11C]-SCH 23390 was also significant in the neocortex where it was shown to represent binding to D1 as well as to 5-HT2 serotonin receptors. High densities of specific benzodiazepine receptor binding were obtained in most neocortical brain areas and in the cerebellum. Using saturation procedures, Bmax and Kd values could be obtained for D2 and benzodiazepine receptors. A comparison of D2 receptor densities in drug-naive schizophrenic patients and healthy volunteers demonstrated similar receptor characteristics in the major basal ganglia in these groups of subjects. Different chemical classes of conventional and unconventional antipsychotic drugs produced a 65%-85% occupancy of D2 receptors when given in clinical doses to schizophrenic patients. High does of diazepam produced a marked occupancy of benzodiazepine receptors during the first hours after oral administration to healthy volunteers. These in vivo methods should be valuable tools for the further analysis of the effects of drug on neuroreceptors in the living brain of neuropsychiatric patients.