IN-VIVO KINETICS OF [F-18] (N-METHYL)BENPERIDOL - A NOVEL PET TRACER FOR ASSESSMENT OF DOPAMINERGIC D2-LIKE RECEPTOR-BINDING

A novel D2-like receptor-binding radioligand, [F-18](N-methyl)benperid ol ([F-18]NMB), was evaluated via positron emission tomographic (PET) imaging studies of baboons. [F-18]NMB rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and striatum-to-cerebell um ratios as high as 35 were achieved after 3 hours. Pretreatment of a n animal with unlabeled receptor-specific antagonists before injection of [F-18]NMB confirmed that the radioligand bound specifically to cen tral D2-like receptors in vivo, and not to S2- or D1-like receptors. U nlabeled eticlopride displaced striatal [F-18]NMB in vivo, showing tha t D2-like binding is reversible. Receptor-binding by the radioligand w as resistant to competitive displacement by synaptic dopamine, as illu strated by the lack of effect of intravenous d-amphetamine on the in v ivo localization of [F-18]NMB. Studies involving sequential intravenou s administration of [F-18]NMB, d-amphetamine, and eticlopride show tha t the radioligand does not undergo agonist-mediated internalization wi th subsequent trapping. The feasibility of applying a three-compartmen t non-steady state model for quantification of [F-18]NMB receptor bind ing was demonstrated. These in vivo characteristics give [F-18]NMB dis tinct advantages over the PET radiopharmaceuticals currently used for clinical investigation of D2-like receptor binding.