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

The pharmacologic characteristics of ^99Tc^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 ^99Tc^m-N-ethyl-N2S2-memantine bound to a single site on NMDA receptor with a Kd of 584.32 nmol/L and a Bmax 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^-0.0016twas established, and the half life was 8.35 min in blood. In conclusion, the new radio-ligand ^99Tc^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.