title: Amyloid-β Deposits Target Efficient Near-Infrared Fluorescent Probes: Synthesis, in Vitro Evaluation, and in Vivo Imaging.
abstract: The formation of extracellular amyloid-β (Aβ) plaques is a common molecular change that underlies several debilitating human conditions, including Alzheimer's disease (AD); however, the existing near-infrared (NIR) fluorescent probes for the in vivo detection of Aβ plaques are limited by undesirable fluorescent properties and poor brain kinetics. In this work, we designed, synthesized, and evaluated a new family of efficient NIR probes that target Aβ plaques by incorporating hydroxyethyl groups into the ligand structure. Among these probes, DANIR 8c showed excellent fluorescent properties with an emission maximum above 670 nm upon binding to Aβ aggregates and also displayed a high sensitivity (a 629-fold increase in fluorescence intensity) and affinity (Kd = 14.5 nM). Because of the improved hydrophilicity that was induced by hydroxyls, 8c displayed increased initial brain uptake and a fast washout from the brain, as well as an acceptable biostability in the brain. In vivo NIR fluorescent imaging revealed that 8c could efficiently distinguish between AD transgenic model mice and normal controls. Overall, 8c is an efficient and veritable NIR fluorescent probe for the in vivo detection of Aβ plaques in the brain.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
authors.forename: Hualong
authors.initials: H
authors.lastname: Fu
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Tu
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities , Wuhan 430074, People's Republic of China.
authors.forename: Jiapei
authors.initials: J
authors.lastname: Dai
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007259:Infrared Rays; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D015394:Molecular Structure
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes