18F-Labeled Benzyldiamine Derivatives as Novel Flexible Probes for Positron Emission Tomography of Cerebral β-Amyloid Plaques
18F-Labeled Benzyldiamine Derivatives as Novel Flexible Probes for Positron Emission Tomography of Cerebral β-Amyloid Plaques
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(18)F 标记的苄二胺衍生物作为新型柔性探针，用于大脑 β-淀粉样蛋白斑块的正电子发射断层扫描
DOI：
10.1021/acs.jmedchem.6b01063
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发表时间：
2016-12-08
影响因子：
7.3
通讯作者：
Zhang, Xianzhong
中科院分区：
文献类型：
--
作者：
Li, Zijing;Zhang, Xuran;Zhang, Xianzhong
利用正电子发射断层扫描 (PET) 对大脑 β-淀粉样蛋白 (Aβ) 斑块进行早期无创可视化是诊断阿尔茨海默病 (AD) 的最可行方法。在本研究中，提出了一系列灵活的苄二胺衍生物（BDA），用于与聚集的β-淀粉样蛋白1-42（A beta（1-42））结合，具有高适应性、高结合亲和力（6.8 +/- 0.6 nM）和快速体内排泄。甲硫基 (12) 和乙氧基 (10) 衍生物进一步用 F-18 直接标记在其苯环上，并作为 A β 斑块成像的 PET 探针进行检查。 [F-18]12 在生物分布研究中显示出 4.87 +/- 0.52% ID/g 的初始摄取并迅速从正常大脑中清除。 MicroPET-CT 成像表明，与商业 [F-18]AV-45 相比，AD 转基因小鼠模型的大脑中 [F-18]12 有足够的保留，但白质摄取较低。我们的实验结果为开发具有灵活框架的靶向配体提供了新的见解，该配体可用作 AD 大脑 PET 成像的有效 A beta 探针。
Early noninvasive visualization of cerebral beta-amyloid (A beta) plaques with positron emission tomography (PET) is the most feasible way to diagnose Alzheimer's disease (AD). In this study, a series of flexible benzyldiamine derivatives (BDA) were proposed for binding to aggregated beta-amyloid 1-42 (A beta(1-42)) with high adaptability, high binding affinity (6.8 +/- 0.6 nM), and rapid body excretion. The methylthio (12) and ethoxyl (10) derivatives were further labeled with F-18 directly on their benzene ring and examined as PET probes for A beta plaque imaging. [F-18]12 displayed 4.87 +/- 0.52% ID/g initial uptake and prompt washout from normal brain in biodistribution studies. MicroPET-CT imaging indicated sufficient retention of [F-18]12 but lower white matter uptake in the brain of an AD transgenic mouse model compared with that of commercial [F-18]AV-45. Our experimental results provide new insights for developing targeting ligands possessing a flexible framework for use as efficient A beta probes for PET imaging of AD brain.