title: 2-Arylbenzothiazoles labeled with [CpRe/99mTc(CO)3] and evaluated as β-amyloid imaging probes.
abstract: An array of complexes,99mTc/Re-labeled cyclopentadienyl tricarbonyl and 2-phenyl/pyridylbenzothiazoles, conjugated through an ester linkage were tested as potential β-amyloid (Aβ) probes for SPECT imaging. The [CpRe/99mTc(CO)3] complexes were prepared by double ligand transfer reactions from ferrocene precursors, and the X-ray structure of one rhenium surrogate revealed a classical "piano stool" like geometry. Several of the rhenium complexes displayed high affinity for Aβ1-42aggregates in in vitro inhibition assays, and they could intensely stain Aβ deposits on brain sections from transgenic mice and Alzheimer's disease (AD) patients. Complex [99mTc]4h strongly binds to Aβ deposits in blood vessels of the brain section of AD patients in in vitro autoradiography. Biodistribution experiments in normal mice revealed that99mTc-labeled tracers exhibited moderate degree of initial brain uptake (0.54%-1.06% ID/g at 2 min). These tracers targeting Aβ plaques of AD patients warrant further structure optimization to improve their ability to penetrate blood-brain barrier, moreover, they may be suitable for developing imaging probes for targeting amyloid aggregates outside of the brain.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR 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, PR China.
authors.forename: Kaixiang
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, PR 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, PR 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, PR China. Electronic address: cmc@bnu.edu.cn.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
mesh_terms: D000368:Aged; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D012211:Rhenium / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D013844:Thiazoles; D012211:Rhenium; D013667:Technetium
keywords: Affinity; Alzheimer's disease; SPECT imaging; β-amyloid