Preliminary assessment of extrastriatal dopamine D-2 receptor binding in the rodent and nonhuman primate brains using the high affinity radioligand, F-18-fallypride

We have identified the value of F-18-fallypride ((S)-N-[(1-allyl-2-pyrrolid inyl)methyl]-5-(3-[F-18]fluoropropyl)-2,3-dimethoxybenzamide as a dopamine D-2 receptor radiotracer for the study of striatal and extrastriatal recept ors. Fallypride exhibits high affinities for D-2 and D-3 subtypes and low a ffinity for D-4 (H-3-spiperone IC(50)s: D-2 = 0.05 nM [rat striata], D-3 = 0.30 nM [SF9 cell lines, rat recombinant], and D-4 = 240 nM [CHO cell lines , human recombinant]). Biodistribution in the rat brain showed localization of F-18-fallypride in striata and extrastriatal regions such as the fronta l cortex, parietal cortex, amygdala, hippocampus, thalamus, and hypothalamu s. In vitro autoradiographic studies in sagittal slices of the rat brain sh owed localization of F-18-fallypride in striatal and several extrastriatal regions, including the medulla. Positron emission tomography (PET) experime nts with F-18-fallypride in male rhesus monkeys were carried out in a PET V I scanner. In several PET experiments, apart from the specific binding seen in the striatum, specific binding of F-18-fallypride was also identified i n extracellular regions tin a lower brain slice, possibly the thalamus). Sp ecific binding in the extrastriata was, however, significantly lower compar ed with that observed in the striata of the monkeys (extrastriata/cerebellu m = 2, striata/cerebellum = 10). Postmortem analysis of the monkey brain re vealed significant F-18-fallypride binding in the striata, whereas binding was also observed in extrastriatal regions such as the thalamus, cortical a reas, and brain stem. (C) 1999 Elsevier Science Inc. All rights reserved.