title: 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-[18F]fluoroethyl)-piperazine and 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-[11C]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. 18F-(half life 109.9 min) obtained by the (p,n) reaction on 18O-enriched water. Labelling with carbon-11 (half life 20.4 min) was achieved by 11C methylation of 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-piperazine with [11C]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.
authors.affiliation: D.R.M., Service Hospitalier Fredéric-Joliot, CEA, Orsay, France.
authors.forename: I
authors.initials: I
authors.lastname: Loustau-Then
authors.forename: M
authors.initials: M
authors.lastname: Ponchant
authors.forename: C
authors.initials: C
authors.lastname: Fuseau
authors.forename: J M
authors.initials: JM
authors.lastname: Kamenka
authors.forename: J
authors.initials: J
authors.lastname: Vignon
authors.forename: C
authors.initials: C
authors.lastname: Crouzel
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000138:chemical synthesis*; D005462:Fluorine Radioisotopes; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D005462:Fluorine Radioisotopes; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D010622:Phencyclidine; D004298:Dopamine