Radio-ligand receptor binding assav in vitro and animal biodistribution in vivo of Tc-99(m)-N-ethyl-N2S2-memantine as a potential NMDA receptor imaging agent

The pharmacologic characteristics of Tc-99(m)-N-ethyl-N2S2-memantine, an NMDA receptor imaging agent, was investigated. It was prepared by a one-step reaction from N-ethyl-N2S2-memantine. The affinity and specificity were determined by radio-ligand receptor binding assay (RRA). Biodistribution in vivo in mice was performed. The results showed that Tc-99(m)-N-ethyl-N2S2-memantine bound to a single site on NMDA receptor with a K-d of 584.32 nmol/L and a B-max of 267.05 nmol/mg. A competitive analysis showed that such specific binding could be inhibited by specific inhibitors of NMDA receptor, such as ketamine and (+)-MK-801. The biodistribution exhibited rapid uptake and favorable retention in mice brains. The major radioactivity was metabolized by the hepatic system. A two-compartment model of C = 4.49e(-0.083t)+1.42e(-0.0016t) was established, and the half life was 8.35 min in blood. In conclusion, the new radio-ligand Tc-99(m)-N-ethyl-N2S2-Memantine has a moderate affinity and specific binding to NMDA receptor, and can easily cross the blood-brain barrier (BBB). Therefore, it may be a potential NMDA receptor imaging agent.