Aurones serve as probes of β-amyloid plaques in Alzheimer’s disease
Aurones serve as probes of β-amyloid plaques in Alzheimer’s disease
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DOI：
10.1016/j.bbrc.2007.06.162
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发表时间：
2007-09
影响因子：
3.1
通讯作者：
M. Ono;Y. Maya;M. Haratake;Kazuhiro Ito;H. Mori;M. Nakayama
中科院分区：
文献类型：
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作者：
M. Ono;Y. Maya;M. Haratake;Kazuhiro Ito;H. Mori;M. Nakayama
合成并表征了一系列新的橙酮衍生物，用于阿尔茨海默病（AD）脑内β-淀粉样斑块的体内成像。当使用Aβ（1−42）聚集体与橙酮衍生物进行体外结合研究时，它们显示出对Aβ（1−42）聚集体的高结合亲和力，Ki值范围为1.2至6.8 nM。当使用双转基因小鼠脑切片进行体外斑块标记时，橙酮衍生物强烈染色β-淀粉样斑块。静脉注射放射性碘标记的橙酮后，在正常小鼠中的生物分布研究显示出高脑摄取（2分钟时为1.9- 4.6%ID/g）和脑快速清除（60分钟时为0.11- 0.26%ID/g），这对于淀粉样蛋白成像剂是非常理想的。本研究的结果表明，新的放射性标记的橙酮可能是有用的淀粉样蛋白成像剂，用于检测AD脑中的β-淀粉样蛋白斑块。
A novel series of aurone derivatives for in vivo imaging of β-amyloid plaques in the brain of Alzheimer’s disease (AD) were synthesized and characterized. When in vitro binding studies using Aβ(1−42) aggregates were carried out with aurone derivatives, they showed high binding affinities for Aβ(1−42) aggregates at the Kivalues ranging from 1.2 to 6.8nM. When in vitro plaque labeling was carried out using double transgenic mice brain sections, the aurone derivatives intensely stained β-amyiloid plaques. Biodistribution studies in normal mice after i.v. injection of the radioiodinated aurones displayed high brain uptake (1.9–4.6% ID/g at 2min) and rapid clearance from the brain (0.11–0.26% ID/g at 60min), which is highly desirable for amyloid imaging agents. The results in this study suggest that novel radiolabeled aurones may be useful amyloid imaging agents for detecting β-amyloid plaques in the brain of AD.