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‐transmission in vivo

A dysfunction of GABAergic neurotransmission is related to diseases such as epilepsy, Huntington‐disease and Parkinson‐syndrome. A new 18 F‐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‐[ 18 F]fluoroethyltosylate or [ 18 F]fluoride. Subsequent cleavage of the ester moiety gave the final product (±)‐(2‐((4‐(2‐[ 18 F]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‐[ 18 F]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.