Novel Radioiodinated 1,3,4-Oxadiazole Derivatives with Improved in Vivo Properties for SPECT Imaging of β-Amyloid Plaques
Novel Radioiodinated 1,3,4-Oxadiazole Derivatives with Improved in Vivo Properties for SPECT Imaging of β-Amyloid Plaques
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新型放射性碘标记 1,3,4-恶二唑衍生物，具有改进的体内特性，可用于 β-淀粉样蛋白斑块的 SPECT 成像
DOI：
10.1039/c3md00189j
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Hideo Saji
中科院分区：
文献类型：
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作者：
Hiroyuki Watanabe;Masahiro Ono;Hiroyuki Kimura;Kenji Matsumura;Masashi Yoshimura;Shimpei Iikuni;Yoko Okamoto;Masafumi Ihara;Ryosuke Takahashi;Hideo Saji
设计并合成了一系列新型的放射性碘标记的3-(5-苯基-1，3，4-恶二唑-2-基)吡啶(1，3，4-PODP)衍生物，用于阿尔茨海默病(AD)脑内β-淀粉样蛋白(A-β)斑块的单光子发射计算机断层扫描成像。在体外结合实验中，1，3，4-PODP衍生物(3和6)与Aβ(1-42)聚集体(分别为25和14 nm)具有较高的亲和力。在体内实验中，[123/125I]3和[123/125I]6在正常小鼠脑内表现出良好的初始摄取和快速洗出，并在Tg2576小鼠中清楚地标记了Aβ斑块。此外，在死后AD脑切片的体外放射自显影中观察到Aβ斑块的特异性标记。这些结果表明，1，3，4-PODP衍生物可能是检测AD脑内Aβ斑块的有用的SPECT探针。
We designed and synthesized a novel series of radioiodinated 3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyridine (1,3,4-PODP) derivatives for imaging β-amyloid (Aβ) plaques in Alzheimer's disease (AD) brains using single photon emission computed tomography (SPECT). In binding experiments in vitro, 1,3,4-PODP derivatives (3 and 6) displayed high affinity for Aβ(1-42) aggregates (25 and 14 nM, respectively). In experiments in vivo, [123/125I]3 and [123/125I]6 displayed good initial uptake into and rapid washout from the brain in normal mice, and clearly labeled Aβ plaques in Tg2576 mice. Furthermore, specific labeling of Aβ plaques was observed in in vitro autoradiography of postmortem AD brain sections. These results suggested that 1,3,4-PODP derivatives may be useful SPECT probes for detecting Aβ plaques in AD brains.