In vivo study of nmda-sensitive glutamate receptor by fluorothienylcycloexylpiperidine, a possible ligand for positron emission tomography

As a preliminary to positron emission tomography (PET) studies of excitatory amino acid neurotransmission, N-methyl-d-aspartate (NMDA)-sensitive glutamate receptors of mice and rats were labelled in vivo with [³H]fluorothienylcycloexylpiperidine (FTCP), which binds to the phencyclidine site of the NMDA receptor. After intravenous injection, the half-life of clearance of authentic FTCP from blood was 4.2 min in mice, 12 min in rats and 45 min in a rhesus monkey. In rodent brain, the specific binding of [³H]FTCP, 10 min after intravenous injection, was 10-20% of the total binding and no regional differences were observed. However, if animals were treated with NMDA intraperitoneally (0.68 mmol/kg), 10 min before injection of [³H]FTCP, a three- to five-fold increase in specific binding was observed in hippocampus, cerebral cortex and striatum but not in cerebellum. Thus, specific binding of [³H]FTCP in vivo revealed the physiological status of the NMDA receptor: in fact, preliminary PET studies with [¹⁸F]FTCP in monkeys indicated increased binding after activation of NMDA receptors. These data suggest that PET with [¹⁸F]FTCP can be a tool to evaluate physiological or pathological modifications of the function of NMDA receptors.