^(125)Ⅰ标记的二噻吩查尔酮类Aβ斑块显像剂的制备与生物评价  

Synthesis and Evaluation of ^(125)Ⅰ Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes

作　　者：彭程[1] 崔孟超[2] 梁志刚[1] 刘亭廷[1] 张晓阳[2] 

机构地区：[1]首都医科大学宣武医院,北京100053 [2]放射性药物教育部重点实验室北京师范大学化学学院,北京100875

出　　处：《同位素》2015年第4期253-258,共6页Journal of Isotopes

摘　　要：合成了溴代、碘代二噻吩查尔酮类Aβ斑块分子探针,体外荧光染色实验证实,两个化合物都能与AD转基因小鼠脑切片上的Aβ斑块特异性结合,竞争结合实验进一步证实与Aβ聚集体有较高的亲和力,Ki值分别为2.33nM和0.88nM。以三丁基锡化合物为标记前体,采用锡-卤交换法进行125I标记,标记率和放化纯度均大于99%,体外放射自显影结果表明,125I标记的二噻吩查尔酮类化合物能够特异性地标记AD转基因小鼠脑切片上Aβ斑块,且与硫磺素-S的染色结果对应。正常小鼠生物分布实验结果表明,该探针穿过血脑屏障的能力较弱,2min时的脑放射性摄取率为1.19%ID/g,但脑清除速率较快。以上结果表明,125I标记的二噻吩查尔酮类化合物具备作为Aβ斑块显像剂的潜力,但还需要进一步的修饰以提高初始脑摄取率。In continuation of the investigation on the bithiophene structure as potential Aβprobes,two halogenated chalcone derivatives containing bithiophene moiety were designed and evaluated as imaging probes for Aβplaques.In vitro fluorescence staining indicated that they could stain Aβplaques in the brain sections of AD model mice specifically,in vitro binding assay further confirmed that they displayed high binding affinities to Aβaggregates（Ki=2.33 nM and 0.88nM）.One radio-iodinated probe,125 I labeleled chalcone derivatives was obtained via iododestannylation reaction with high radiochemi-cal yield and purity（〉99%）.Moreover,the 125 I labeling compound displayed specific labeling of Aβplaques in the brain sections of AD model mice with low background,and the specific labeling could be confirmed by thioflavin-S staining.In vivo biodistribution in normal mice indicated that the 125 I labeling compound exhibited low initial brain uptake（1.19%ID/g at 2 min）and rapid clearance.These preliminary results suggest that 125 I labeling compound may serve as novel Aβimaging probe,although further modifications are needed to improve initial brain uptake.

关 键 词：阿尔兹海默症 Aβ斑块 放射自显影 生物分布 

分 类 号：TL923[核科学技术—核燃料循环与材料]