Stereoselective binding of 11C-raclopride in living human brain--a search for extrastriatal central D2-dopamine receptors by PET

Abstract

The selective D2-dopamine receptor antagonist raclopride and its pharmacologically inactive (R)-enantiomer FLB472 were labelled with 11C and used in a study with positron emission tomography to examine the stereoselectivity of 11C-raclopride binding to central D2-dopamine receptors in three healthy men. After the injection of 11C-raclopride, there was a high accumulation of radioactivity in the dopamine-rich basal ganglia, whereas after the injection of 11C-FLB472 there was no such accumulation of radioactivity. Thus, the binding of 11C-raclopride is stereoselective. Distribution ratios [radioactivity in a brain region/"free" (not protein-bound) radioactivity in plasma] were calculated for the two enantiomers to study regional differences in the accumulation of radioactivity. The distribution ratios in white matter were similar for the two enantiomers. In the putamen, a three to four-fold higher distribution ratio was found for 11C-raclopride than for 11C-FLB472, reflecting the presence of specific binding of 11C-raclopride binding to D2-dopamine receptors in the basal ganglia. In the temporal and frontal cortices the distribution ratios were, however, only a few per cent higher for 11C-raclopride than for 11C-FLB472, indicating that if D2-dopamine receptors are present in the human neocortex, then their density is indeed very low.