高等学校化学学报

高等学校化学学报 ›› 2010, Vol. 31 ›› Issue (12): 2413.

• 研究论文 • 上一篇    下一篇

多巴胺D2受体显像剂125I-DMAIBZM的合成及生物分布实验

李光慧,盛许晶,朱建华   

  1. 复旦大学药学院, 上海  201203
  • 收稿日期:2010-02-09 修回日期:2010-05-12 出版日期:2010-12-10 发布日期:2010-12-06
  • 通讯作者: 朱建华 E-mail:072103152@fudan.edu.cn
  • 作者简介:朱建华, 男, 教授, 博士生导师, 主要从事放射性药物的研究.
  • 基金资助:

    国家“九七三”计划项目(批准号: 2007CB935800)资助.

Synthesis and Biodistribution of  125I-DMAIBZM for Dopamine D2 Receptor Imaging

LI Guang-Hui, SHENG Xu-Jing, ZHU Jian-Hua*   

  1. School of Pharmacy, Fudan University, Shanghai 201203, China
  • Received:2010-02-09 Revised:2010-05-12 Online:2010-12-10 Published:2010-12-06
  • Contact: ZHU Jian-Hua E-mail:072103152@fudan.edu.cn
  • About author:朱建华, 男, 教授, 博士生导师, 主要从事放射性药物的研究.
  • Supported by:

    Major State Basic Research Development Program

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摘要： 为提高苯甲酰胺类衍生物（S）-N-（1-乙基-2-吡咯烷基）甲基-4-氨基-2-甲氧基苯酰胺（ABZM）的入脑量，对其结构进行改造，得到了新的化合物（S）-4-二甲氨基-N-（1-乙基-2-吡咯烷基）甲基-2-甲氧基苯酰胺（DMABZM）.通过Idogen法对DMABZM进行标记得到标记化合物125I-DMAIBZM，标记率为74%，放化纯度达到99%． 体外放射配基结合实验测得DMABZM的IC50为2.9589×10-7 mol?L-1，表明它与能与多巴胺D2受体特异性结合且具有较高的亲和力，在小鼠体内的分布实验中，该标记物纹状体/小脑的比值可达6.5左右，说明了该标记化合物与纹状体的结合有较高的特异性和亲和力．125I-DMAIBZM的脂溶性显著大于125I-AIBZM，入脑量有较大的提高．结论：125I（123I）-DMAIBZM有望用于多巴胺D2受体的显像．

关键词: 多巴胺D2受体, 125I ；受体显像

Abstract: To improve the brain uptake of the benzamide compound 125I-AIBZM (S)- 5-125I -N-(1-ethyl-2-pyrrolidinyl) methyl-4-amine -2-methoxy- benzamide, the structure modification was performed resulting in a new compound 125I-DMAIBZM ((S)-5-125I-Iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-4-dimethyl- amine-2-methoxy-benzamide) produced. Labeling was achieved by Iodogen method, with 74% radiochemical yield. After HPLC purification, radiochemical purity >99% was obtained. The receptor binding affinity of DMABZM to rat brain membrane（IC50为2.9589×10-7 mol?L-1）have shown high affinity to dopamine D2 receptor. The mice biodistribution data for 125I-DMAIBZM (the ratio striatum/cerebellum>6.5) indicates a good distribution in striatum with high specificity and affinity. The lipophilicity of 125I-DMAIBZM is significantly higher than that of 125I-AIBZM. Conclusion: 125I（123I）-DMAIBZM is in a promise state for Dopamine D2 receptor Imaging.

Key words: Dopamine D2 receptor, 125I；receptor imaging

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