In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist 11C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate

Abstract

The in vitro autoradiographic binding characteristics as well as in vivo imaging characteristics of a dopamine D2 receptor agonist, (R,S)-2-(N-propyl- N-1'-11C-propyl)amino-5-hydroxytetralin (11C-5-OH-DPAT), were studied. In 3H-spiperone assays using rat striata, 5-OH-DPAT exhibited an affinity of IC50 = 2.5 nM. In vitro autoradiographs in rat brain slices with 11C-5- OH-DPAT revealed selective binding to the dopaminergic regions in the striata which was displaceable by sulpiride. Varying concentrations of dopamine displaced this selective binding of 11C-5-OH-DPAT to the striata in rat brain slices. This selective binding to the striata was also removed in the presence of the GTP analog, 5'-guanylylimidodiphosphate, indicative of the binding of 11C-5-OH-DPAT to the high-affinity state of the D2 receptor. Ex vivo autoradiographic study in rats exhibited selective binding of 11C-5- OH-DPAT to the striata. A PET study in a rhesus monkey showed selective localization of 11C-5-OH-DPAT in the striata and the ratio between striata and cerebellum approached approximately 2 at 40 min postinjection. (C) 2000 Wiley-Liss, Inc.