Lockhart A, Lamb J R, Osredkar T, Sue L I, Joyce J N, Ye L, Libri V, Leppert D, Beach T G
GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK.
Brain. 2007 Oct;130(Pt 10):2607-15. doi: 10.1093/brain/awm191. Epub 2007 Aug 13.
The in vivo imaging probe [11C]-PIB (Pittsburgh Compound B, N-methyl[11C]2-(4'-methylaminophenyl-6-hydroxybenzathiazole) is under evaluation as a key imaging tool in Alzheimer's disease (AD) and to date has been assumed to bind with high affinity and specificity to the amyloid structures associated with classical plaques (CPs), one of the pathological hallmarks of the disease. However, no studies have systematically investigated PIB binding to human neuropathological brain specimens at the tracer concentrations achieved during in vivo imaging scans. Using a combination of autoradiography and histochemical techniques, we demonstrate that PIB, in addition to binding CPs clearly delineates diffuse plaques and cerebrovascular amyloid angiopathy (CAA). The interaction of PIB with CAA was not fully displaceable and this may be linked to the apolipoprotein E-epsilon4 allele. PIB was also found to label neurofibrillary tangles, although the overall intensity of this binding was markedly lower than that associated with the amyloid-beta (Abeta) pathology. The data provide a molecular explanation for PIB's limited specificity in diagnosing and monitoring disease progression in AD and instead indicate that the ligand is primarily a non-specific marker of Abeta-peptide related cerebral amyloidosis.
体内成像探针[11C]-PIB（匹兹堡化合物B，N-甲基[11C]2-(4'-甲基氨基苯基-6-羟基苯并噻唑)）正在作为阿尔茨海默病（AD）的关键成像工具进行评估，迄今为止，人们一直认为它能以高亲和力和特异性与与经典斑块（CPs）相关的淀粉样蛋白结构结合，而经典斑块是该疾病的病理特征之一。然而，尚无研究系统地研究在体内成像扫描期间达到的示踪剂浓度下PIB与人神经病理学脑标本的结合情况。通过结合放射自显影和组织化学技术，我们证明PIB除了结合CPs外，还能清晰地勾勒出弥漫性斑块和脑血管淀粉样血管病（CAA）。PIB与CAA的相互作用不能完全被取代，这可能与载脂蛋白E-ε4等位基因有关。还发现PIB能标记神经原纤维缠结，尽管这种结合的总体强度明显低于与淀粉样β蛋白（Aβ）病理学相关的强度。这些数据为PIB在AD诊断和监测疾病进展方面特异性有限提供了分子解释，相反表明该配体主要是Aβ肽相关脑淀粉样变性的非特异性标志物。
