Gradients of dopamine D 1- and D 2/3-binding sites in the basal ganglia of pig and monkey measured by PET

Abstract

The distributions of dopamine D 1 and D 2/3 binding sites in living brain have not been compared directly using positron emission tomography (PET). To map these binding sites, we first optimized methods for the assay of dopamine receptors in brain of Göttingen miniature pigs. The binding potentials ( pB) of [ 11C]NNC 112 for dopamine D 1 receptors and [ 11C]raclopride for dopamine D 2/3 receptors were calculated in pig striatum volumes of interest using metabolite corrected arterial inputs or using cerebellum as a non-binding reference region. Depending upon the method for quantitation, the pB for [ 11C]NNC 112 was 1.2–5.1 in pig striatum, whereas the pB for [ 11C]raclopride was 1.0–1.8. We used the reference tissue method of Logan to calculate pB maps for the two tracers. The maps were co-registered to the common stereotaxic space for the pig brain and normalized to a global mean for pB in striatum; t-maps showed that dopamine D 1 binding was relatively more abundant in the ventral–anterior striatum of the pig, while dopamine D 2/3 binding was greater in the dorsal striatum. Similar comparisons were made for the pBs of [ 11C]Sch 23390 for dopamine D 1 receptors and for [ 11C]raclopride in the brain of six rhesus monkeys. The magnitudes of pB for both binding sites in monkey brain were close to those in the pig. Consistent with the pig results, there were distinct gradients in the distributions of the two binding sites in monkey brain: D 1 binding predominated in the ventral striatum, whereas D 2/3 binding was relatively greater in the dorsal-posterior striatum. Gradients of dopamine receptor concentration within the striatum may be a general phenomenon of mammalian brain.