In vivo detection of amyloid-β deposits by near-infrared imaging using an oxazine-derivative probe
In vivo detection of amyloid-β deposits by near-infrared imaging using an oxazine-derivative probe
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DOI：
10.1038/nbt1085
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发表时间：
2005-05-01
影响因子：
46.9
通讯作者：
Gremlich, HU
中科院分区：
文献类型：
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作者：
Hintersteiner, M;Enz, A;Gremlich, HU
由于阿尔茨海默病的发病机制与淀粉样β -肽不溶性聚集体的形成有关，能够在体内直接、无创地观察斑块生长的方法将有利于生物医学研究。在此我们描述了近红外荧光恶嗪染料AOI987的合成与特性，它能轻易穿透完整的血脑屏障并与淀粉样斑块结合。通过近红外荧光成像，我们证明了AOI987与APP23转基因小鼠体内的淀粉样斑块有特异性相互作用，这通过对脑切片的死后分析得到了证实。定量分析显示，随着动物斑块负荷的增加，荧光信号强度增加，并且在9个月及以上年龄的APP23转基因小鼠中观察到AOI987有显著结合。因此，AOI987是一种有吸引力的探针，可用于在阿尔茨海默病动物模型中非侵入性地监测疾病进展，并评估潜在的阿尔茨海默病药物对斑块负荷的影响。
As Alzheimer's disease pathogenesis is associated with the formation of insoluble aggregates of amyloid beta-peptide, approaches allowing the direct, noninvasive visualization of plaque growth in vivo would be beneficial for biomedical research. Here we describe the synthesis and characterization of the near-infrared fluorescence oxazine dye AOI987, which readily penetrates the intact blood-brain barrier and binds to amyloid plaques. Using near-infrared fluorescence imaging, we demonstrated specific interaction of AOI987 with amyloid plaques in APP23 transgenic mice in vivo, as confirmed by postmortem analysis of brain slices. Quantitative analysis revealed increasing fluorescence signal intensity with increasing plaque load of the animals, and significant binding of AOI987 was observed for APP23 transgenic mice aged 9 months and older. Thus, AOI987 is an attractive probe to noninvasively monitor disease progression in animal models of Alzheimer disease and to evaluate effects of potential Alzheimer disease drugs on the plaque load.