Ishiki A, Harada R, Okamura N, Tomita N, Rowe C C, Villemagne V L, Yanai K, Kudo Y, Arai H, Furumoto S, Tashiro M, Furukawa K
Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Eur J Neurol. 2017 Jan;24(1):130-136. doi: 10.1111/ene.13164. Epub 2016 Oct 31.
Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [ F]THK-5351, which we have recently developed.
Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [ H]THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [ F]THK-5351. To detect amyloid-β deposition, PET imaging with Pittsburgh compound B was also performed.
Autoradiography in the brain sections of patients with PSP demonstrated [ H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [ F]THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP.
We conclude that [ F]THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.
在许多神经退行性疾病中，致病蛋白聚集体的可视化对于阐明发病机制和进行准确诊断至关重要。微管结合蛋白tau的聚集体是神经退行性疾病中最重要的致病分子之一。进行性核上性麻痹（PSP）的特征是tau蛋白在基底神经节和脑干等特定区域沉积。我们试图用一种新型正电子发射断层扫描（PET）示踪剂[F]THK-5351来检测活体PSP患者大脑中的tau病变，该示踪剂是我们最近研发的。
PSP患者的石蜡包埋脑切片用于[H]THK-5351放射自显影和免疫组织化学分析。9名健康对照者、13名阿尔茨海默病患者和3名PSP患者参与了这项使用[F]THK-5351的PET研究。为了检测β淀粉样蛋白沉积，还进行了匹兹堡化合物B的PET成像。
PSP患者脑切片的放射自显影显示[H]THK-5351与tau沉积物具有高度选择性结合。虽然PSP患者在颞叶皮质未表现出明显的[F]THK-5351滞留，但在苍白球和中脑观察到示踪剂滞留显著更高。相比之下，匹兹堡化合物B的淀粉样蛋白成像显示PSP患者的大脑皮质没有明显的积聚。
我们得出结论，[F]THK-5351 PET有可能用于检测PSP中tau病变的区域脑分布，从而有助于与tau蛋白相关的神经退行性疾病的鉴别诊断。
