Synthesis and evaluation of new ¹⁸F-labelled thienylcyclohexylpiperidine (TCP) analogues as radioligands for the NMDA receptor-channel complex

We have synthesized new fluorine-18 labelled derivatives of thienylcyclohexylpiperidine (TCP), a non-competitive antagonist of NMDA receptor, which binds to the phencyclidine (PCP) binding site located within the receptor-associated ion channel. The mesylate precursors for (1S*,2R*)-2-(hydroxymethyl)- and (1S*,2R*)-2-(methoxymethyoxymethyl)-1-(N-piperidyl)-1-[2-(2'-[¹⁸F] fluoroethyl)thiophenyl]cyclohexane, [¹⁸F]4 and [¹⁸F]19, respectively, were prepared from 2-hydroxycyclo-hexanone. Radiochemical syntheses were done by displacement of the mesylates by [¹⁸F]fluoride ion with no-carrier-added [K/2.2.2]⁺¹⁸F in 4-4.5% radiochemical yields with specific activity of >31 GBq/mol. In the biodistribution studies with [¹⁸F]4 and [¹⁸F]19, no selective accumulation of radioactivity was observed. Low affinities of these ligands to the NMDA receptor were also shown in in vitro binding experiments.