Evaluation of 5-[18F]Fluoropropylepidepride as a potential pet radioligand for imaging dopamine D2 receptors

✍ Scribed by Robert M. Kessler; John R. Votaw; Tomas de Paulis; Daniel R. Bingham; M. Sib Ansari; N. Scott Mason; George Holburn; Dennis E. Schmidt; Delicia B. Votaw; Ronald G. Manning; Michael H. Ebert

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 875 KB
• Volume: 15
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/syn.890150302

✦ Synopsis

Abstract

This study evaluated the utility of (S)‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐(3‐[^18^F]fluoropropyl)‐2,3‐dimethoxybenzamide ([^18^F]fluoropropylepidepride), [^18^F]5‐FPrEpid, as a ligar d for PET studies of cerebral dopamine D2 receptors. The in vitro affinity for the rat striatal dopamine D2 receptor, K~D~ 138 pM, was determined by Scatchard analysis of in vitro binding to rat striatal homogenate. 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 [^18^F]5‐FPrEpid by a variety of neurotransmitter ligands. Only dopamine D2 ligands displaced [^18^F]5‐FPrEpid with high affinity. Positron tomographic imaging studies in primates of [^18^F]5‐FPrEpid demonstrated a stable striatal uptake. of 0.02% injected dose/ml for up to 5 h after injection. The striatal: cerebellar ratio 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 raclopride (2.5 mg/kg) to cerebellar levels with a t~1/2~ of washout of 9 or 15 min. Striatal uptake was mildly susceptible to displacement by d‐amphetamine (1–2 mg/kg) released endogenous dopamine; d‐amphetamine administration produced a 10%/h increase in the rate of striatal washout. Although uptake in the striatum is reversible, an equilibrium between receptor bound [^18^F]5‐FPrEpid in striatum and [^18^F]5‐FPrEpid in plasma is not reached within 5 h postinjection. © 1993 Wiley‐Liss. Inc.