Cui Mengchao, Li Zijing, Tang Ruikun, Jia Hongmei, Liu Boli
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Xinjiekouwai Street 19#, Beijing 100875, PR China.
Eur J Med Chem. 2011 Jul;46(7):2908-16. doi: 10.1016/j.ejmech.2011.04.015. Epub 2011 Apr 12.
In continuation of our investigation on the bithiophene structure as potential β-amyloid probes, a series of (E)-5-styryl-2,2'-bithiophene (SBTP) derivatives was designed and synthesized. In vitro binding showed that all of them displayed high binding affinities to Aβ(1-42) aggregates (K(i)=0.10-41.05nM). Moreover, two radio-iodinated probes, [(125)I]-(E)-5-(4-iodostyryl)-2,2'-bithiophene ([(125)I]8) and [(125)I]-(E)-5-iodo-5'-(4-methoxystyryl)-2,2'-bithiophene ([(125)I]31) were prepared. Both of them displayed specific labeling of Aβ plaques in the brain sections of AD model mice with low background. In vivo biodistribution in normal mice indicated that [(125)I]8 exhibited high initial brain uptake (2.11% ID/g at 2 min) and rapid clearance (0.41% ID/g at 30 min). These preliminary results suggest that SBTP derivatives may be served as novel β-amyloid imaging probes.
作为我们对二噻吩结构作为潜在β-淀粉样蛋白探针研究的延续，设计并合成了一系列（E）-5-苯乙烯基-2,2'-二噻吩（SBTP）衍生物。体外结合实验表明，它们对Aβ(1-42)聚集体均表现出高结合亲和力（K(i)=0.10 - 41.05 nM）。此外，制备了两种放射性碘化探针，[(125)I]-(E)-5-(4-碘苯乙烯基)-2,2'-二噻吩([(125)I]8)和[(125)I]-(E)-5-碘-5'-(4-甲氧基苯乙烯基)-2,2'-二噻吩([(125)I]31)。它们在AD模型小鼠脑切片中均显示出对Aβ斑块的特异性标记，背景较低。正常小鼠体内生物分布表明，[(125)I]8表现出高初始脑摄取（2分钟时为2.11% ID/g）和快速清除（30分钟时为0.41% ID/g）。这些初步结果表明，SBTP衍生物可能作为新型β-淀粉样蛋白成像探针。
