title: 18F-Labeled Benzyldiamine Derivatives as Novel Flexible Probes for Positron Emission Tomography of Cerebral β-Amyloid Plaques.
abstract: 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 (Aβ1-42) 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 with18F 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.
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University , Xiamen, Fujian 361102, China.
authors.forename: Zijing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University , Xiamen, Fujian 361102, China.|Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Xuran
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital , Fuzhou 350001, China.|Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University , Fuzhou 350001, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Pan
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University , Xiamen, Fujian 361102, China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D013329:Structure-Activity Relationship
chemical_list: D001593:Benzyl Compounds; D005462:Fluorine Radioisotopes; D015335:Molecular Probes