Kung Mei-Ping, Weng Chi-Chang, Lin Kun-Ju, Hsiao Ing-Tsung, Yen Tzu-Chen, Wey Shiaw-Pyng
Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chang Gung Med J. 2012 May-Jun;35(3):211-8. doi: 10.4103/2319-4170.106151.
The formation and deposition of β-amyloid (Aβ) plaques are the earliest pathological changes in Alzheimer's disease (AD). Molecular imaging of Aβ plaques could serve as a surrogate marker in early diagnosis and neuropathogenesis studies of AD. Several radionuclide labeled ligands have recently been developed for noninvasive visualization of Aβ plaques in the brains of AD patients using single photon emission computed tomography or positron emission tomography (PET). There has been rapid progress in the field of imaging for plaque pathology. AV-45 was the first plaque imaging agent to enter multi-center, investigational new drug clinical trials in the US, and has now been studied in dozens of trials with more than 1,000 subjects ranging from cognitively normal individuals to those with AD dementia. "Imaging to autopsy" phase III studies further confirmed and validated the specific imaging signal correlated to the plaque burden in living subjects. With these promising and confirmed characteristics of AV-45, the Alzheimer's Disease Neuroimaging Initiative (ADNI) under common consensus decided on AV-45 as the emerging standard PET imaging agent for evaluating the progression of plaque pathology in patients with AD or mild cognition impairment, and even healthy controls. With the wide availability of AV-45 for plaque imaging, the ultimate goal of the ADNI is global clinical trials for disease detection and progression. This review presents recent experience with Aβ-targeting radiotracers at Chang Gung University and Chang Gung Memorial Hospital.
β-淀粉样蛋白(Aβ)斑块的形成和沉积是阿尔茨海默病(AD)最早出现的病理变化。Aβ斑块的分子成像可作为AD早期诊断和神经病理发生研究中的替代标志物。最近已开发出几种放射性核素标记的配体,用于使用单光子发射计算机断层扫描或正电子发射断层扫描(PET)对AD患者大脑中的Aβ斑块进行无创可视化。斑块病理学成像领域取得了迅速进展。AV-45是首个进入美国多中心、研究性新药临床试验的斑块成像剂,目前已在数十项试验中对1000多名受试者进行了研究,这些受试者涵盖认知正常个体到患有AD痴呆症的患者。“成像到尸检”的III期研究进一步证实并验证了与活体受试者斑块负荷相关的特定成像信号。鉴于AV-45具有这些有前景且已得到证实的特性,阿尔茨海默病神经影像学计划(ADNI)在共同共识下决定将AV-45作为评估AD或轻度认知障碍患者甚至健康对照者斑块病理进展的新兴标准PET成像剂。随着AV-45广泛用于斑块成像,ADNI的最终目标是进行全球疾病检测和进展的临床试验。本综述介绍了长庚大学和长庚纪念医院在靶向Aβ放射性示踪剂方面的最新经验。