Novel Radioiodinated Aurones as Probes for SPECT Imaging of β-Amyloid Plaques in the Brain
Novel Radioiodinated Aurones as Probes for SPECT Imaging of β-Amyloid Plaques in the Brain
复制标题
DOI：
10.1021/bc8003292
复制
发表时间：
2009-01-01
影响因子：
4.7
通讯作者：
Nakayama, Morio
中科院分区：
文献类型：
--
作者：
Maya, Yoshifumi;Ono, Masahiro;Nakayama, Morio
我们报告了一系列新的放射性碘标记的金酮衍生物作为探针，用于使用单光子发射计算机断层扫描（SPECT）对阿尔茨海默病（AD）患者大脑中的A β斑块进行成像。在体外结合实验中，橙酮衍生物对A β聚集体显示出非常好的亲和力（Ki = 1.1至3.4 nM）。通过相应的三丁基锡衍生物的碘脱锡基化反应，成功地制备了无载体添加的放射性碘标记的橙酮。在使用正常小鼠的生物分布实验中，橙酮衍生物显示出高脑摄取（2 min时为1.7-4.5% ID/g）和快速脑清除（30 min时为0.1-0.4% ID/g），尤其是[I-121]15。此外，在使用[I-121]15的死后AD脑切片的体外放射自显影中观察到特异性斑块标记信号。[I-121]15可能是检测AD脑内A β斑块的有效SPECT显像剂。
We report a novel series of radioiodinated aurone derivatives as probes for imaging A beta plaques in the brains of patients with Alzheimer's disease (AD) using single photon emission computed tomography (SPECT). In binding experiments in vitro, aurone derivatives showed very good affinity for A beta aggregates (K-i = 1.1 to 3.4 nM). No-carrier-added radioiodinated aurones were successfully prepared through an iododestannylation reaction from the corresponding tributyltin derivatives, In biodistribution experiments using normal mice, aurone derivatives displayed high brain uptake (1.7-4.5% ID/g at 2 min) and rapid clearance from the brain (0.1-0.4% ID/g at 30 min), especially [I-121]15. Furthermore, a specific plaque labeling signal was observed in in vitro autoradiography of postmortem AD brain sections using [I-121]15. [I-121]15 may be a useful SPECT imaging agent for detecting A beta plaques in the brain of AD.