title: 99mTc(CO)3-Labeled Benzothiazole Derivatives Preferentially Bind Cerebrovascular Amyloid: Potential Use as Imaging Agents for Cerebral Amyloid Angiopathy.
abstract: Cerebral amyloid angiopathy (CAA) is a disorder affecting the elderly that is characterized by amyloid-β (Aβ) deposition in blood vessel walls of the brain. A series of 99mTc(CO)3-labeled benzothiazole derivatives as potential SPECT imaging probes for cerebrovascular Aβ deposition is reported. Rhenium surrogate displayed high affinities to Aβ aggregates with Ki values ranging from 106 to 42 nM, and they strongly stained Aβ deposits in transgenic mice (Tg) and Alzheimer's disease (AD) patients. In vitro autoradiography on brain sections of Tg and AD patients confirmed that [99mTc]24 possessed sufficient affinity for Aβ plaques, and [99mTc]24 could only label Aβ deposition in blood vessels but not Aβ plaques in the parenchyma of the brain of AD patients. Moreover, [99mTc]24 possessed favorable initial uptake (1.21% ID/g) and fast blood washout (blood2 min/blood60 min=23) in normal mice. These preliminary results suggest that [99mTc]24 may be used as an Aβ imaging probe for the detection of CAA.
authors.affiliation: †Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Jia
authors.affiliation: †Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.affiliation: ‡Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, P. R. 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, P. R. China.
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D052160:Benzothiazoles / Q000737:chemistry* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D017556:Technetium Compounds / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D019275:Radiopharmaceuticals; D017556:Technetium Compounds; C005465:benzothiazole
keywords: CAA; affinity; amyloid-β; autoradiography; selectivity