EVALUATION OF 5-[F-18]FLUOROPROPYLEPIDEPRIDE AS A POTENTIAL PET RADIOLIGAND FOR IMAGING DOPAMINE D2 RECEPTORS

This study evaluated the utility of l]-5-(3-[F-18]fluoropropyl)-2,3-di methoxybenzamide ([F-18]fluoropropylepidepride), [F-18]5-FPrEpid, as a ligand for PET studies of cerebral dopamine D2 receptors. The in vitr o affinity for the rat striatal dopamine D2 receptor, K-D 138 pM, was determined by Scatchard analysis of in vitro binding to rat striatal h omogenate. The apparent lipophilicity, log k(w) 1.6, was measured with reverse phase HPLC at pH 7.5. The receptor specificity was determined by competitive displacement of [F-18]5-FPrEpid by a variety of neurot ransmitter ligands. Only dopamine D2 ligands displaced [F-18]5-FPrEpid with high affinity. Positron tomographic imaging studies in primates of[F-18]5-FPrEpid demonstrated a stable striatal uptake of 0.02% injec ted dose/ml for up to 5 h after injection. The striatal: cerebellar ra tio increased from 2 at 15 min, to 7 at 200 min, and to 10 at 300 min. Striatal uptake was displaceable by haloperidol (1 mg/kg) or raclopri de (2.5 mg/kg) to cerebellar levels with a t(1/2) of washout of 9 or 1 5 min. Striatal uptake was mildly susceptible to displacement by d-amp hetamine (1-2 mg/kg) released endogenous dopamine; d-amphetamine admin istration produced a 10%h increase in the rate of striatal washout. Al though uptake in the striatum is reversible, an equilibrium between re ceptor bound [F-18]5-FPrEpid in striatum and [F-18]5-FPrEpid in plasma is not reached within 5 h postinjection. (c) 1993 Wiley-Liss, Inc.