Serdons K, Verduyckt T, Vanderghinste D, Borghgraef P, Cleynhens J, Van Leuven F, Kung H, Bormans G, Verbruggen A
Laboratory for Radiopharmacy, Faculty of Pharmaceutical Sciences, K.U. Leuven, O&N2, Herestraat 49-Bus 821, 3000 Leuven, Belgium.
Eur J Med Chem. 2009 Apr;44(4):1415-26. doi: 10.1016/j.ejmech.2008.09.038. Epub 2008 Oct 7.
Pittsburgh Compound-B (PIB) is currently being evaluated clinically for in vivo visualization of amyloid plaques in patients with Alzheimer's disease (AD). We have synthesized three structural isomers of 6-hydroxy-2-(4'-aminophenyl)-1,3-benzothiazole, performed radiolabelling with carbon-11 and investigated their in vivo and in vitro properties. Specific binding to amyloid plaques was demonstrated in vitro using post-mortem brain homogenates of AD patients, transgenic AD mice brain sections and post-mortem human AD brain sections. In normal mice, initial brain uptake (at 2 min p.i.) was high and was followed by a fast wash-out. The three structural analogues have a high potential as tracer agents for in vivo visualization of amyloid plaques in AD patients.
匹兹堡化合物-B(PIB)目前正在临床上进行评估,用于阿尔茨海默病(AD)患者体内淀粉样斑块的可视化。我们合成了6-羟基-2-(4'-氨基苯基)-1,3-苯并噻唑的三种结构异构体,用碳-11进行放射性标记,并研究了它们的体内和体外性质。使用AD患者的死后脑匀浆、转基因AD小鼠脑切片和死后人类AD脑切片在体外证明了与淀粉样斑块的特异性结合。在正常小鼠中,初始脑摄取(注射后2分钟)很高,随后快速清除。这三种结构类似物作为AD患者体内淀粉样斑块可视化的示踪剂具有很高的潜力。