Positron-Emitting N-[¹⁸F]Fluoroalkyl and [¹⁸F]Fluoropyrrolidinyl Analogues of Eticlopride as Potential in vivo Radioligands for Dopamine D2 Receptors

Abstract

N-Fluoroalkyl and 4-fluoropyrrolidinyl eticlopride analogues with high affinity toward central nervous system dopamine D2 receptors in vitro were labelled with positron emitting fluorine-18 (t_1/2=110 min), and their in vivo biodistribution was investigated in rats. N-[¹⁸F]Fluoro-ethyl and -propyl eticlopride derivatives showed poor in vivo selectivity in the rat brain. On the other hand, 4-[¹⁸F]fluoropyrrolidinyl eticlopride exhibited almost constant and relatively high striatal concentration. The striata/cerebellar radioactivity ratio, which corresponds to the ratio of a brain D2 receptor-rich to poor region, gradually increased to 5.2-6.4, 90 min after the injection. The striatal accumulation was selectively inhibited by pre-injection of haloperidol, a dopamine D2 antagonist, without affecting accumulation in other tissues. Thus, the selective striatal accumulation of 4-[¹⁸F]fluoropyrrolidinyl eticlopride in striatal tissue appears to be due to the specific binding to dopamine D2 receoptors.