A PET-study of [11C]FLB 457 binding to extrastriatal D2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients

Abstract

We recently developed [¹¹C]FLB 457 a substituted benzamide with the very high affinity of 20 pM for D₂-dopamine receptors in vitro. The aim of the present exploratory study was to examine the anatomical distribution of [¹¹C]FLB 457 binding in the human brain and to determine extrastriatal D₂-receptor occupancy in antipsychotic drug-treated patients. [¹¹C]raclopride was used to obtain reference values for D₂-dopamine receptor occupancy in the putamen. After IV injection of [¹¹C]FLB 457 there was a high concentration of radioactivity, not only in the caudate putamen but also in the thalamus and the temporal cortex. The concentration of radioactivity in the frontal cortex, the substantia nigra and the colliculi was slightly higher than in the cerebellum. Pretreatment with haloperidol and fluphenazine indicated that [¹¹C]FLB 457 binding in extrastriatal regions to a high degree represents specific binding to D₂-dopamine receptors. The D₂-occupancy in antipsychotic drug-treated patients was on the same level in the thalamus and the temporal cortex as that determined with [¹¹C]raclopride in the putamen. The study shows that [¹¹C]FLB 457 has potential for quantitative PET-examination of D₂-dopamine receptors in man.