Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
Molecules. 2012 Apr 10;17(4):4252-65. doi: 10.3390/molecules17044252.
We report the synthesis and biological evaluation of novel (E)-5-styryl-1H-indole and (E)-6-styrylquinoline derivatives as probes for imaging β-amyloid (Aβ) plaques. These derivatives showed binding affinities for Aβ₁₋₄₀ aggregates with K(i) values varying from 4.1 to 288.4 nM. (E)-5-(4-iodostyryl)-1H-indole (8) clearly stained Aβ plaques in the brain sections of Alzheimer's disease (AD) model mice (APP/PS1). Furthermore, autoradiography for [¹²⁵I]8 displayed intense and specific labeling of Aβ plaques in the brain sections mentioned above with low background. In biodistribution experiments using normal mice [¹²⁵I]8 showed high initial brain uptake followed by rapid washout (4.27 and 0.64% ID/g at 2 and 30 min post injection, respectively). These findings suggests that [¹²³I]8 may be a potential SPECT imaging agent for detecting Aβ plaques in AD brain.
我们报告了新型（E）-5-（苯乙烯基）-1H-吲哚和（E）-6-（苯乙烯基）喹啉衍生物的合成和生物学评价，这些化合物可作为β-淀粉样蛋白（Aβ）斑块成像的探针。这些衍生物对 Aβ₁₋₄₀ 聚集物具有结合亲和力，K(i) 值范围为 4.1 到 288.4 nM。（E）-5-（4-碘代苯乙烯基）-1H-吲哚（8）可清晰染色阿尔茨海默病（AD）模型小鼠大脑切片中的 Aβ 斑块。此外，[¹²⁵I]8 的放射自显影术在上述大脑切片中显示出 Aβ 斑块的强烈和特异性标记，背景较低。在使用正常小鼠的生物分布实验中，[¹²⁵I]8 显示出较高的初始脑摄取，随后迅速清除（分别在 2 和 30 分钟时为 4.27%和 0.64% ID/g）。这些发现表明，[¹²³I]8 可能是一种用于检测 AD 大脑中 Aβ 斑块的潜在 SPECT 成像剂。
