6533b820fe1ef96bd1279899

RESEARCH PRODUCT

Radiosynthesis of (±)-(2-((4-(2-[18F]fluoro-ethoxy)phenyl)bis(4-methoxy-phenyl)methoxy)ethylpiperidine-3-carboxylic acid: a potential GAT-3 PET ligand to study GABAergic neuro-transmissionin vivo

subject

description

A dysfunction of GABAergic neurotransmission is related to diseases such as epilepsy, Huntington-disease and Parkinson-syndrome. A new 18F-fluorine labelled GABA transporter ligand for the GABA-transporter subtype GAT-3 was developed which may allow the in vivo visualisation of GABAergic neurotransmission. The precursors ethyl (2-(4-hydroxyphenyl)bis(4-methoxyphenyl)-methoxy)ethyl)-piperidine-3-carboxylate and ethyl(2-((4-(2-tosylethoxy)phenyl)-bis(4-methoxyphenyl)-methoxy) ethyl)-piperidine3-carboxylate were synthesised and labelled by the use of 2-[18F]fluoroethyltosylate or [18F]fluoride. Subsequent cleavage of the ester moiety gave the final product (±)-(2-((4-(2-[18F]fluoroethoxy)phenyl)bis(4-methoxy-phenyl)methoxy)ethyl)piperidine-3-carboxylic acid in a decay corrected yield of 33–36%. Preliminary biodistribution kinetics were determined with BALB/c mice ex vivo for brain, liver, kidney, spleen, blood and bone. (2-((4-(2-[18F]fluoroethoxy)-phenyl)bis(4-methoxyphenyl)methoxy)-ethyl) piperidine-3-carboxylic acid showed a maximum brain uptake after 1 h p.i. of about 0.3% ID/g. Copyright © 2001 John Wiley & Sons, Ltd.