SYNTHESIS AND BIODISTRIBUTION OF 2 POTENTIAL PET RADIOLIGANDS FOR DOPAMINE REUPTAKE SITES - NO-CARRIER-ADDED 4-(2-[F-18]FLUOROETHYL) AND 4-[C-11]METHYL BTCP-PIPERAZINE

Radioligands that specifically target dopamine uptake sites can provid e a means of determining dopamine fiber loss at intrastriatal mesencep halic grafts in Parkinsonian patients, using Positron Emission Tomogra phy (PET). The BTCP derivative, ophenyl)cyclohexyl]-4-(2-hydroxyethyl) -piperazine, shows in vitro high affinity and selectivity for the dopa mine transporter, To evaluate the potential of such a compound as a po tential dopaminergic PET tracer the positron emitting analogues, enyl) cyclohexyl]-4-(2-[F-18]fluorethyl)-piperazine and b)thiophenyl)cyclohe xyl]-4-[C-11]methylpiperazine, were synthesized. Radiofluorination was carried out by the reaction of thiophenyl)cyclohexyl]-4-(2-chlorethyl )-piperazine with cyclotron-produced n.c.a. F-18-(half life 109.9 min) obtained by the (p,n) reaction on O-18 enriched water. Labelling with carbon-11 (half life 20.4 min) was achieved by C-11 methylation of 1- [1-(2-benzo(b)thiophenyl)cyclohexyl]-piperazine with [C-11]methyl iodi de. After intravenous administration to rats these two compounds enter the brain, but despite their high in vitro affinity they display a hi gh non specific binding in vivo which greatly limits their use as radi oligands. (C) 1997 Elsevier Science Inc.