摘要
用99Tcm标记新的美金刚胺(memantine)衍生物N-[2-(N-(2-巯基乙基))氨基乙酰基]-N-(2-巯基乙基)-3,5-二甲基金刚烷胺基乙酰胺(N2S2-memantine,简称NCAM),并通过优化标记条件获得放射化学纯度达95%以上的标记化合物99Tcm-NCAM。脂溶性实验测得其脂水分配系数lgP=1.90。放射性受体结合分析显示,其与N-甲基-D-门冬氨酸(NMDA)受体结合具有饱和性,根据受体B区理论编制的计算机程序求出NMDA受体结合参数最大结合容量Bmax=56.8μmol/g,平衡解离常数Kd=706.3 nmol/L,特异性NMDA受体拮抗剂能阻断其与NMDA受体的结合。结果显示99Tcm-NCAM与NMDA受体结合具有中等程度的亲和力和结合特异性,具有较好的脂溶性,易透过血脑屏障,有可能成为一种新的NMDA受体显像剂。
A new radio- tine N2S2-memantine （ ligand ^99Tc^m-NCAM was synthesized by labeling a derivative of meman- N- [- 2- （ N- （2-mercapotoethyl） ） aminoformylmethyl l-N- （ 2-mercapotoethyl）-3, 5-dimethyladamantyl aminoacetamide, NCAM）, and its radioehemical purity was greater than 95 % determined by TLC under optimized labeling conditions. The radio-ligand receptor binding assay was shown that the binding of radio-ligand ^99Tc^m-NCAM to NMDA receptor was saturable with a dissociation constant Kd of 706.3 nmol/L and a Bmax of 56.8 umol/g calculated by a computer program written based on the receptor theory in B region. The competitive analysis show that such specific binding could be inhibited by specific inhibitors of NMDA receptor. Its oil/water partition coefficient is 1.90. In conclusion, the new radio-ligand ^99Tc^m-NCAM, which was systhesized by the method of directly labelling NCAM with ^99Tc^m, has a moderate affinity and specific binding to NMDA receptor, and can easily transported through the blood-brain barrier（BBB）. Therefore, it may be a potential NMDA receptor imaging agent.
出处
《核化学与放射化学》
CAS
CSCD
北大核心
2009年第2期98-103,共6页
Journal of Nuclear and Radiochemistry
基金
国家自然科学基金资助项目(30770602)
江苏省卫生厅重大项目资助(K200512)
