The pharmacologic characteristics of ^(99)Tc^m-N-ethyl-N_2S_2-memantine,an NMDA receptor imaging agent,was investigated.It was prepared by a one-step reaction from N-ethyl-N_2S_2-memantine.The affinity and specificity...The pharmacologic characteristics of ^(99)Tc^m-N-ethyl-N_2S_2-memantine,an NMDA receptor imaging agent,was investigated.It was prepared by a one-step reaction from N-ethyl-N_2S_2-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 ^(99)Tc^m-N-ethyl-N_2S_2-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 ^(99)Tc^m-N-ethyl-N_2S_2-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.展开更多
基金Supported by National Natural Science Foundation(No30770602)Jiangsu Natural Science Foundation(No BK2008111)
文摘The pharmacologic characteristics of ^(99)Tc^m-N-ethyl-N_2S_2-memantine,an NMDA receptor imaging agent,was investigated.It was prepared by a one-step reaction from N-ethyl-N_2S_2-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 ^(99)Tc^m-N-ethyl-N_2S_2-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 ^(99)Tc^m-N-ethyl-N_2S_2-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.
