In vivo detection of prion amyloid plaques using [11C]BF-227 PET
In vivo detection of prion amyloid plaques using [11C]BF-227 PET
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DOI：
10.1007/s00259-009-1314-7
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发表时间：
2010-05-01
影响因子：
9.1
通讯作者：
Doh-ura, Katsumi
中科院分区：
文献类型：
--
作者：
Okamura, Nobuyuki;Shiga, Yusei;Doh-ura, Katsumi
脑内病理性朊蛋白（PrP）的体内检测对于传染性海绵状脑病（TSE）的诊断具有潜在的应用价值。然而，没有非侵入性的生前手段检测病理性PrP沉积在大脑中。本研究采用正电子发射断层扫描（PET）技术，以BF-227为示踪剂，采用放射自显影和荧光显微镜技术，研究了BF-227与PrP淀粉样蛋白的结合能力。5例TSE患者（包括3例Gerstmann-Straussler-Scheinker病（GSS）患者和2例散发性Creutzfeldt-Jakob病（CJD）患者）接受了[C-11]BF-227 PET扫描。结果进行了比较，从10个正常对照组和17例阿尔茨海默病（AD）患者的数据。计算区域与脑桥的标准化摄取值比率作为BF-227保留的指数。BF-227与PrP斑块的结合使用来自尸检证实的GSS病例的脑样本来证实。在临床PET研究中，与正常对照组的相应组织相比，在GSS患者的小脑、丘脑和外侧颞叶皮质中检测到显著更高的BF-227保留。与AD患者相比，GSS患者还显示出BF-227在小脑、丘脑和内侧颞叶皮质中的更高保留。尽管[C-11]BF-227是脑淀粉样变性的非特异性成像标记物，但基于示踪剂的区域分布，它可用于GSS人脑中PrP斑块的体内检测。PET淀粉样蛋白成像可能为某些形式的TSE的早期诊断和非侵入性疾病监测提供一种手段。
In vivo detection of pathological prion protein (PrP) in the brain is potentially useful for the diagnosis of transmissible spongiform encephalopathies (TSEs). However, there are no non-invasive ante-mortem means for detection of pathological PrP deposition in the brain. The purpose of this study is to evaluate the amyloid imaging tracer BF-227 with positron emission tomography (PET) for the non-invasive detection of PrP amyloid in the brain.The binding ability of BF-227 to PrP amyloid was investigated using autoradiography and fluorescence microscopy. Five patients with TSEs, including three patients with Gerstmann-Straussler-Scheinker disease (GSS) and two patients with sporadic Creutzfeldt-Jakob disease (CJD), underwent [C-11]BF-227 PET scans. Results were compared with data from 10 normal controls and 17 patients with Alzheimer's disease (AD). The regional to pons standardized uptake value ratio was calculated as an index of BF-227 retention.Binding of BF-227 to PrP plaques was confirmed using brain samples from autopsy-confirmed GSS cases. In clinical PET study, significantly higher retention of BF-227 was detected in the cerebellum, thalamus and lateral temporal cortex of GSS patients compared to that in the corresponding tissues of normal controls. GSS patients also showed higher retention of BF-227 in the cerebellum, thalamus and medial temporal cortex compared to AD patients. In contrast, the two CJD patients showed no obvious retention of BF-227 in the brain.Although [C-11]BF-227 is a non-specific imaging marker of cerebral amyloidosis, it is useful for in vivo detection of PrP plaques in the human brain in GSS, based on the regional distribution of the tracer. PET amyloid imaging might provide a means for both early diagnosis and non-invasive disease monitoring of certain forms of TSEs.