In vivo visualization of α-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzoxazole positron emission tomography in multiple system atrophy
In vivo visualization of α-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzoxazole positron emission tomography in multiple system atrophy
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DOI：
10.1093/brain/awq091
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发表时间：
2010-06-01
期刊：
影响因子：
14.5
通讯作者：
Itoyama, Yasuto
中科院分区：
文献类型：
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作者：
Kikuchi, Akio;Takeda, Atsushi;Itoyama, Yasuto
多系统萎缩的组织病理学标志是细胞内包涵体的出现，称为胶质细胞质包涵体，其主要由α-突触核蛋白原纤维组成。在多系统萎缩中，α-突触核蛋白沉积的体内可视化应用于诊断和评估治疗和病理进展的严重程度。因为2-[2-（2-dimethylaminothiazol-5-yl）ethenyl]-6-[2-（fluoro）ethoxy] benzoxazole可以染色死后脑中含有α-synuclein的胶质细胞胞质内含物，我们比较了8例多系统萎缩病例与年龄匹配的正常对照的碳11标记的2-[2-（2-dimethylaminothiazol-5-yl）ethenyl]-6-[2-（fluoro）ethoxy] benzoxazole正电子发射断层扫描结果。正电子发射断层扫描数据显示皮质下白色物质的高分布体积（未校正P < 0.001），壳核和后扣带回皮质（未校正P < 0.005），苍白球，初级运动皮层和前扣带皮层与正常对照组相比，多系统萎缩组中黑质（未校正P <0.05）和黑质（未校正P <0.01）。它们与多系统萎缩中神经胶质细胞质内含物丰富的脑区一致，因此，碳-11-标记的2-[2-（2-二甲基氨基噻唑-5-基）乙烯基]-6-[2-（氟）乙氧基]苯并恶唑正电子发射断层扫描是一种有前途的替代标记物，用于监测活脑中细胞内α-突触核蛋白沉积。
The histopathological hallmark of multiple system atrophy is the appearance of intracellular inclusion bodies, named glial cytoplasmic inclusions, which are mainly composed of alpha-synuclein fibrils. In vivo visualization of alpha-synuclein deposition should be used for the diagnosis and assessment of therapy and severity of pathological progression in multiple system atrophy. Because 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole could stain alpha-synuclein-containing glial cytoplasmic inclusions in post-mortem brains, we compared the carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography findings of eight multiple system atrophy cases to those of age-matched normal controls. The positron emission tomography data demonstrated high distribution volumes in the subcortical white matter (uncorrected P < 0.001), putamen and posterior cingulate cortex (uncorrected P < 0.005), globus pallidus, primary motor cortex and anterior cingulate cortex (uncorrected P < 0.01), and substantia nigra (uncorrected P < 0.05) in multiple system atrophy cases compared to the normal controls. They were coincident with glial cytoplasmic inclusion-rich brain areas in multiple system atrophy and thus, carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography is a promising surrogate marker for monitoring intracellular alpha-synuclein deposition in living brains.