National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Adv Exp Med Biol. 2019;1184:217-230. doi: 10.1007/978-981-32-9358-8_18.
The deposition of fibrillar tau aggregates has been implicated in Alzheimer's disease (AD) and allied neurodegenerative disorders collectively referred to as tauopathies. Growing non-clinical and clinical evidence has supported intimate links between tau fibrillogenesis and neuronal deteriorations, rationalizing the development of imaging agents for tau fibrils to gain etiological insights into tauopathies and to facilitate diagnostic and therapeutic approaches to these diseases. Radiochemicals derived from three major chemotypes were initially applied to positron emission tomography (PET) studies of human subjects, demonstrating their utility for capturing AD-type tau deposits with reasonably high contrast. Meanwhile, these tracers suffered substantial off-target binding in the brain and did not offer sensitive detection of tau lesions in a large proportion of non-AD tauopathies. To overcome such drawbacks, 'second-generation' tau PET probes have been generated and examined in clinical settings. These tracers have enabled specific assays of AD tau pathologies, and a novel radiocompound developed by our research group has been shown to produce high contrasts for AD and non-AD tau aggregates, potentially allowing diagnostic evaluations of diverse tauopathies on an individual basis.
纤维状 tau 聚集物的沉积与阿尔茨海默病 (AD) 以及统称为 tau 病的相关神经退行性疾病有关。越来越多的非临床和临床证据支持 tau 纤维形成与神经元恶化之间的密切联系，这使得 tau 纤维成像剂的开发具有合理性，以深入了解 tau 病的病因，并促进这些疾病的诊断和治疗方法。最初应用于正电子发射断层扫描 (PET) 研究人体的三种主要化学型放射性化学物质，证明它们具有合理高对比度捕获 AD 型 tau 沉积物的能力。同时，这些示踪剂在大脑中存在大量的非靶标结合，并且不能敏感地检测到大部分非 AD tau 病中的 tau 病变。为了克服这些缺点，已经生成并在临床环境中检查了“第二代”tau PET 探针。这些示踪剂能够特异性检测 AD tau 病变，并且我们研究小组开发的一种新型放射性化合物已被证明可产生 AD 和非 AD tau 聚集物的高对比度，有可能允许根据个体情况对各种 tau 病进行诊断评估。
