Synthesis and evaluation of new 18 F‐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 (1 S *, 2 R *)‐2‐(hydroxymethyl)‐ and (1 S *, 2 R *)‐2‐(methoxymethyoxy‐methyl)‐1‐( N ‐piperidyl)‐1‐[2‐(2′‐[ 18 F]fluoroethyl)thiophenyl]cyclohexane, [ 18 F] 4 and [ 18 F] 19, respectively, were prepared from 2‐hydroxycyclo‐hexanone. Radiochemical syntheses were done by displacement of the mesylates by [ 18 F]fluoride ion with no‐carrier‐added [K/2.2.2] +18 F − in 4–4.5% radiochemical yields with specific activity of >31 GBq/mol. In the biodistribution studies with [ 18 F] 4 and [ 18 F] 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.