Synthesis and biodistribution of two potential PET radioligands for dopamine reuptake sites: No-carrier-added 4-(2-[18F]fluoroethyl) and 4-[11C]methyl BTCP-piperazine

Abstract Radioligands that specifically target dopamine uptake sites can provide a means of determining dopamine fiber loss at intrastriatal mesencephalic grafts in Parkinsonian patients, using Positron Emission Tomography (PET). The BTCP derivative, 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-(2-hydroxyethyl)-piperazine, shows in vitro high affinity and selectivity for the dopamine transporter. To evaluate the potential of such a compound as a potential dopaminergic PET tracer the positron-emitting analogues, 1-[1-(2-benzo (b)thiophenyl)cyclohexyl]-4-(2-[ 18 F]fluoroethyl)-piperazine and 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-[ 11 C]methylpiperazine, were synthesized. Radiofluorination was carried out by the reaction of 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-(2-chloroethyl)-piperazine with cyclotron-produced n.c.a. 18 F-(half life 109.9 min) obtained by the (p,n) reaction on 18 O-enriched water. Labelling with carbon-11 (half life 20.4 min) was achieved by 11 C methylation of 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-piperazine with [ 11 C]methyl iodide. After intravenous administration to rats these two compounds enter the brain, but despite their high in vitro affinity they display a high non specific binding in vivo which greatly limits their use as PET radioligands.