A PET STUDY OF [C-11]FLB-457 BINDING TO EXTRASTRIATAL D-2-DOPAMINE RECEPTORS IN HEALTHY-SUBJECTS AND ANTIPSYCHOTIC DRUG-TREATED PATIENTS

We recently developed [C-11]FLB 457 a substituted benzamide with the v ery high affinity of 20 pM for D-2-dopamine receptors in vitro. The ai m of the present exploratory study was to examine the anatomical distr ibution of [C-11]FLB 457 binding in the human brain and to determine e xtrastriatal D-2-receptor occupancy in antipsychotic drug-treated pati ents. [C-11]raclopride was used to obtain reference values for D-2-dop amine receptor occupancy in the putamen, After IV injection of [C-11]F LB 457 there was a high concentration of radioactivity, not only in th e caudate putamen but also in the thalamus and the temporal cortex, Th e concentration of radioactivity in the frontal cortex, the substantia nigra and the colliculi was slightly higher than in the cerebellum. P retreatment with haloperidol and fluphenazine indicated that [C-11]FLB 457 binding in extrastriatal regions to a high degree represents spec ific binding to D-2-dopamine receptors. The D-2-occupancy in antipsych otic drug-treated patients was on the same level in the thalamus and t he temporal cortex as that determined with [C-11]raclopride in the put amen. The study shows that [C-11]FLB 457 has potential for quantitativ e PET-examination of D-2-dopamine receptors in man.