Radiosynthesis of (+/-)-(2-((4-(2-[F-18]fluoroethoxy)phenyl)bis(4-methoxy-phenyl) methoxy)ethylpiperidine-3-carboxylic acid: a potential GAT-3 PET ligand to study GABAergic neuro-transmission in vivo

A dysfunction of GABAergic neurotransmission is related to diseases such as epilepsy, Huntington-disease and Parkinson-syndrome. A new F-18-fluorine l abelled GABA transporter ligand for the GABA-transporter subtype GAT-3 was developed which may allow the in vivo visualisation of GABAergic neurotrans mission. The precursors ethyl (2-(4-hydroxyphenyl)bis (4-methoxyphenyl)-met hoxy)ethyl)-piperidine-3-carboxylate and ethyl(2-((4(2-tosylethoxy)phenyl)- bis(4-methoxyphenyl)-methoxy) ethyl)piperidine-3-carboxylate were synthesis ed and labelled by the use of 2-[F-18]fluoroethyltosylate or [18F]fluoride, Subsequent cleavage of the ester moiety gave the final product (+/-)-(2-(( 4-(2-[F-18]fluoroethoxy)phenyl) bis(4-methoxy-phenyl)methoxy)ethyl)piperidi ne-3-carboxylic acid in a decay corrected yield of 33-36%. Preliminary biod istribution kinetics were determined with BALB/c mice ex vivo for brain., l iver, kidney. spleen, blood and bone. (2-((4-(2-[F-18]fluoroethoxy)-phenyl) bis(4-methoxyphenyl)methoxy)-ethyl) piperidine-3-carboxylic acid showed a m aximum brain uptake after 1 h p.i. of about 0.3% ID/g. Copyright (C) 2001 J ohn Wiley & Sons, Ltd.