SPECIFIC, REVERSIBLE BINDING OF [F-18] BENPERIDOL TO BABOON D-2 RECEPTORS - PET EVALUATION OF AN IMPROVED F-18 LABELED LIGAND

[F-18]Benperidol ([F-18]BP), a positron-emitting analogue of the dopam inergic D-2 antagonist benperidol, was evaluated as a radiopharmaceuti cal for use with positron emission tomography (PET). PET imaging of ba boons after i.v. injection of [F-18]BP indicated that the radiofluorin ated ligand rapidly localized in vivo within dopaminergic receptor-ric h cerebral tissues, and that selective disposition was retained for ov er 2 h. Pretreatment of an animal with unlabeled receptor-specific ant agonists prior to injection of [F-18]BP confirmed that the radioligand bound specifically to central D-2 receptors in vivo, and not to S-2 o r D-1 receptors. [F-18]BP bound to D-2 receptors in a reversible manne r; unlabeled eticlopride displaced D-2 receptor-bound [F-18]BP in vivo . The radioligand was metabolized in the periphery to polar metabolite s which are not expected to cross the blood-brain barrier. [F-18]BP ha s advantages over other tracers as a radiopharmaceutical for PET study of central D-2 receptor activity, and can be applied for noninvasive evaluation of the interaction of unlabeled drugs with central D-2 rece ptor sites.