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    NMDA受体显像剂99Tcm-NCAM的制备和受体结合分析

    Radiochemical Synthesis and Radio-Ligand Receptor Binding Assay of 99Tcm-NCAM as a Potential NMDA Receptor Imaging Agent

      摘要
    • 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lg P=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=56.8 μmol/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。

       

      Abstract: A new radio-ligand 99Tcm-NCAM was synthesized by labeling a derivative of memantine N2S2-memantine (N2-(N-(2-mercapotoethyl))aminoformylmethylN-(2-mercapotoethyl)-3, 5-dimethyladamantyl aminoacetamide, NCAM), and its radiochemical 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 99Tcm-NCAM to NMDA receptor was saturable with a dissociation constant Kd of 706.3 nmol/L and a Bmaxof 56.8 μmol/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 99Tcm-NCAM, which was systhesized by the method of directly labelling NCAM with 99Tcm, 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.

       

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