title: Synthesis and evaluation of novel benzothiazole derivatives based on the bithiophene structure as potential radiotracers for beta-amyloid plaques in Alzheimer's disease.
abstract: In this study, six novel benzothiazole derivatives based on the bithiophene structure were developed as potential beta-amyloid probes. In vitro binding studies using Abeta aggregates showed that all of them demonstrated high binding affinities with K(i) values ranged from 0.11 to 4.64nM. In vitro fluorescent staining results showed that these compounds can intensely stained Abeta plaques within brain sections of APP/PS1 transgenic mice, animal model for AD. Two radioiodinated compounds [(125)I]-2-(5'-iodo-2,2'-bithiophen-5-yl)-6-methoxybenzo[d]thiazole [(125)I]10 and [(125)I]-2-(2,2'-bithiophen-5-yl)-6-iodobenzo[d]thiazole [(125)I]13 were successfully prepared through an iododestannylation reaction. Furthermore, in vitro autoradiography of the AD model mice brain sections showed that both [(125)I]10 and [(125)I]13 labeled the Abeta plaques specifically with low background. In vivo biodistribution studies in normal mice indicated that [(125)I]13 exhibited high brain uptake (3.42% ID/g at 2min) and rapid clearance from the brain (0.53% ID/g at 60min), while [(125)I]10 showed lower brain uptake (0.87% ID/g at 2min). In conclusion, these preliminary results of this study suggest that the novel radioiodinated benzothiazole derivative [(125)I]13 may be a candidate as an in vivo imaging agent for detecting beta-amyloid plaques in the brain of AD patients.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Cui
authors.forename: Zi-Jing
authors.initials: ZJ
authors.lastname: Li
authors.forename: Rui-Kun
authors.initials: RK
authors.lastname: Tang
authors.forename: Bo-Li
authors.initials: BL
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001345:Autoradiography; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012995:Solubility; D013876:Thiophenes / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D007457:Iodine Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D013876:Thiophenes