18F-Labeled Benzyldiamine Derivatives as Novel Flexible Probes for Positron Emission Tomography of Cerebral β-Amyloid Plaques

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• 作者：Zijing Li ; Xuran Zhang ; Xiaoyang Zhang ; Mengchao Cui ; Jie Lu ; Xiaodong Pan ; Xianzhong Zhang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：December 8, 2016
• 年：2016
• 卷：59
• 期：23
• 页码：10577-10585
• 全文大小：506K
• ISSN：1520-4804

文摘

Early noninvasive visualization of cerebral β-amyloid (Aβ) 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 β-amyloid 1–42 (Aβ_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 ¹⁸F directly on their benzene ring and examined as PET probes for Aβ plaque imaging. [¹⁸F]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 [¹⁸F]12 but lower white matter uptake in the brain of an AD transgenic mouse model compared with that of commercial [¹⁸F]AV-45. Our experimental results provide new insights for developing targeting ligands possessing a flexible framework for use as efficient Aβ probes for PET imaging of AD brain.