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

β-淀粉样蛋白(A-β)多肽聚集体在脑内的形成和积聚是阿尔茨海默病(AD)发生发展的关键因素。淀粉样斑块的体内成像可能导致早期发现AD并监测AD治疗的进展和有效性。体内成像探针显示出对Aβ聚集体的高结合亲和力和高脑穿透性，对于阿尔茨海默病淀粉样斑块的成像是必不可少的。近年来，许多基于刚果红和硫代黄素的显像剂被报道为潜在的显像剂。我们已经合成并评价了标记有^&lt；123&gt；I和^&lt；11&gt；C的苯并呋喃和二苯乙烯衍生物作为用于阿尔茨海默病淀粉样斑块成像的PET和SPECT探针。这一结果促使我们进一步寻找具有高贵核心结构的有效且更实用的淀粉样蛋白成像探针。在对机制…的研究中，已有研究表明某些黄酮类化合物可能与淀粉样蛋白斑块具有结合亲和力黄酮类化合物抗淀粉样变活性的背后更具说服力。本研究设计合成了一系列的黄酮衍生物。以过氧化氢为催化剂，通过碘去单宁化反应制备放射性碘化黄酮类化合物。这些黄酮类化合物的对数pc值在1.9~2.7之间，在最适范围内。使用预先形成的合成Aβ聚集体的体外结合试验评估了淀粉样斑块的结合亲和力。某些化合物与A-β(1-40)和A-β(1-42)聚集体的结合亲和力从13 nm到77 nm不等。当用死后的AD脑切片进行体外斑块标记时，所有的黄酮类化合物不仅强烈染色，淀粉样斑块，而且脑血管淀粉样斑块也被染色。用标准的生物分布研究评价放射性碘标记的黄酮衍生物在正常小鼠体内的药代动力学特性。几种化合物在注射后2分钟显示出高脑摄取率，从3.2%到4.1%ID/g。放射性从脑中迅速洗出(30min时为0.5-1.9%ID/g)，这是淀粉样蛋白显像剂非常需要的。这些结果表明，这类放射性碘标记的黄酮类化合物可能是潜在的淀粉样斑块显像剂。较少

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