In Vivo Imaging of β-Amyloid Plaques in Alzheimer's Disease Brains.

脑内β-淀粉样蛋白（Aβ）聚集体的形成和积累是阿尔茨海默病（AD）发生发展的关键因素。淀粉样蛋白斑块的体内成像可能导致AD的早期检测和监测AD治疗的进展和有效性。显示出对Aβ聚集体的高结合亲和力和高脑穿透性的体内成像探针对于阿尔茨海默病中淀粉样蛋白斑块的成像是必不可少的。近年来，许多基于刚果红和硫磺素的药物被报道为潜在的显像剂。我们已经合成并评估了苯并呋喃和二苯乙烯衍生物标记的^<123>I和^<11>C作为PET和SPECT探针成像淀粉样斑块在阿尔茨海默病。这一结果促使我们进一步寻找有效的、更实用的、具有高贵核心结构的淀粉样蛋白成像探针。 ...更多信息 黄酮抗淀粉样蛋白生成活性背后的机理。本研究设计并合成了一系列黄酮衍生物。以过氧化氢为催化剂，通过碘代脱锡反应制备了放射性碘标记黄酮。这些黄酮的log PC值从1.9到2.7不等，跨越了最佳范围。通过使用预形成的合成Aβ聚集体的体外结合测定来评估淀粉样蛋白斑块的结合亲和力。某些化合物对Aβ（1-40）和Aβ（1-42）聚集体的结合亲和力在13 nM至77 nM之间变化。当使用死后AD脑切片进行体外斑块标记时，所有黄酮不仅强烈染色淀粉样斑块，而且还染色脑血管淀粉样蛋白。放射性碘标记的黄酮衍生物的体内药代动力学特性进行了评价，在正常小鼠与标准的生物分布研究。几种化合物在注射后2分钟显示出范围为3.2至4.1%ID/g的高脑摄取。放射性迅速从脑中洗出（30分钟时0.5-1.9%ID/g），这对于淀粉样蛋白成像剂是高度期望的。这些结果表明，类放射性碘标记的黄酮可能是有用的候选人作为淀粉样斑块的潜在显像剂。少

Formation and accumulation of β-amyloid (Aβ) peptide aggregates in the brain are critical factors in the development and progression of Alzheimer's disease (AD). In vivo imaging of amyloid plaques may lead to early detection of AD and monitoring the progression and effectiveness of AD treatment. In vivo imaging probes, showing high binding affinity for Aβ aggregates, and high brain penetrations, are essential for imaging of amyloid plaques in Alzheimer's disease. Recently, many agents based on Congo red and thioflavin have been reported as potential imaging agents. We have synthesized and evaluated benzofuran and stilbene derivatives labeled with ^<123>I and ^<11>C as PET and SPECT probes for imaging amyloid plaques in Alzheimer's disease. The results has prompted us to further search for effective and more practical amyloid imaging probe having a noble core structure.It has been previously shown that some flavones may have binding affinity to amyloid plaques in research into the mecha … More nism behind the anti-amyloidogenic activity of flavones. In this study, a series of flavone derivatives was designed and synthesized. Preparation of radioiodinated flavone was carried out by an iododestannylation reaction catalyzed by hydrogen peroxide. The log PC value of these flavones varied from 1.9 to 2.7, spanning the optimum range. The binding affinities for amyloid plaques were assessed by in vitro binding assay using pre-formed synthetic Aβ aggregates. The binding affinities of some compounds for Aβ (1-40) and Aβ (1-42) aggregates varied from 13nM to 77nM. When in vitro plaque labeling was carried out using post-mortem AD brain sections, all flavones intensely stained not only, amyloid plaques, but also cerebrovascular amyloids. The in vivo pharmacokinetic properties of radioiodinated flavone derivatives were evaluated in normal mice with standard biodistribution studies. Several compounds displayed high brain uptakes ranging from 3.2 to 4.1%ID/g at 2min post injection. The radioactivity was washed out from the brain rapidly (0.5-1.9%ID/g at 30min), which is highly desirable for amyloid imaging agents. These results suggest that the classes of radioiodinated flavones may be useful candidates as potential imaging agents for amyloid plaques. Less