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

作者：Li, Zijing^*; Zhang, Xuran; Zhang, Xiaoyang; Cui, Mengchao; Lu, Jie; Pan, Xiaodong^*; Zhang, Xianzhong

来源：Journal of Medicinal Chemistry, 2016, 59(23): 10577-10585.

DOI：10.1021/acs.jmedchem.6b01063

• MILD COGNITIVE IMPAIRMENT
• IN-VIVO
• ALZHEIMER-DISEASE
• THIOFLAVIN-T
• F-18-FLUTEMETAMOL
• NEURODEGENERATION
• BURDEN

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.

• 出版日期2016-12-8
• 单位福建医科大学; 厦门大学; 北京师范大学