In vivo kinetics of [¹⁸F](N-methyl)benperidol: A novel PET tracer for assessment of dopaminergic D2-like receptor binding

A novel D2-like receptor-binding radioligand, [¹⁸F](N- methyl)benperidol ([¹⁸F]NMB), was evaluated via positron emission tomographic (PET) imaging studies of ba boons. [¹⁸F]NMB rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and striatum-to- cerebellum ratios as high as 35 were achieved after 3 hours. Pretreatment of an animal with unlabeled receptor-specific antagonists be fore injection of [¹⁸F]NMB confirmed that the radioligand bound specifically to central D2- like receptors in vivo, and not to S2- or D1-like receptors. Unlabeled eticlopride displaced striatal [¹⁸F]NMB in vivo, showing that D2-like binding is reversible. Receptor-binding by the radioligand was resistant to competitive displacement by synaptic dopamine, as illustrated by the lack of effect of intravenous d-amphetamine on the in vivo localization of [¹⁸F]NMB. Studies involving sequential intravenous administration of [¹⁸F]NMB, d-amphetamine, and eticlopride show that the radioligand does not undergo agonist mediated internalization with subsequent trapping. The feasibility of applying a three-compartment non-steady state model for quantification of [¹⁸F]NMB receptor binding was demonstrated. These in vivo characteristics give [¹⁸F]NMB distinct advantages over the PET radiopharmaceuticals currently used for clinical investigation of D2-like receptor binding.