Bacskai Brian J, Hickey Gregory A, Skoch Jesse, Kajdasz Stephen T, Wang Yanming, Huang Guo-Feng, Mathis Chester A, Klunk William E, Hyman Bradley T
Department of Neurology/Alzheimer's Disease Research Laboratory, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA.
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12462-7. doi: 10.1073/pnas.2034101100. Epub 2003 Sep 29.
The lack of a specific biomarker makes preclinical diagnosis of Alzheimer's disease (AD) impossible, and it precludes assessment of therapies aimed at preventing or reversing the course of the disease. The development of a tool that enables direct, quantitative detection of the amyloid-beta deposits found in the disease would provide an excellent biomarker. This article demonstrates the real-time biodistribution kinetics of an imaging agent in transgenic mouse models of AD. Using multiphoton microscopy, Pittsburgh compound B (PIB) was imaged with sub-microm resolution in the brains of living transgenic mice during peripheral administration. PIB entered the brain quickly and labeled amyloid deposits within minutes. The nonspecific binding was cleared rapidly, whereas specific labeling was prolonged. WT mice showed rapid brain entry and clearance of PIB without any binding. These results demonstrate that the compound PIB has the properties required for a good amyloid-imaging agent in humans with or at risk for AD.
缺乏特异性生物标志物使得阿尔茨海默病（AD）的临床前诊断无法实现，也妨碍了对旨在预防或逆转疾病进程的疗法进行评估。开发一种能够直接、定量检测该疾病中发现的β-淀粉样蛋白沉积物的工具将提供一种出色的生物标志物。本文展示了一种成像剂在AD转基因小鼠模型中的实时生物分布动力学。利用多光子显微镜，在外周给药期间，以亚微米分辨率对活体转基因小鼠大脑中的匹兹堡化合物B（PIB）进行成像。PIB迅速进入大脑，并在数分钟内标记淀粉样蛋白沉积物。非特异性结合迅速清除，而特异性标记持续存在。野生型小鼠显示PIB快速进入大脑并清除，无任何结合。这些结果表明，化合物PIB具有作为人类AD患者或有AD风险者良好淀粉样蛋白成像剂所需的特性。
