摘要
阿尔茨海默病(AD)的主要病理特征是由β淀粉样蛋白(Aβ)和tau蛋白过度磷酸化的神经原纤维缠结(NFTs)组成的老年斑(SPS)。这些特点都与胆碱能功能障碍有关。而导致AD的发生的过程是是复杂的、多因素的,并且AD的病因并不明确,显然,AD是一种需要结合协同方法治疗的多方面的疾病。因为目前AD明确诊断是由大脑尸检实现,因此,为了检测和监测AD病的演变和评价治疗的疗效,新型无创影像诊断技术亟待研究开发。正电子发射断层扫描(PET)是一种利用正电子放射性同位素(碳11,氟18,铜64,镓68……)标记,以高空间分辨率和独特的敏感性实现体内细胞代谢的可视化的核分子成像技术,而单光子发射计算机断层扫描(SPECT)使用放射性同位素锝99或碘123。除了作为诊断的有力工具(主要是18F-脱氧葡萄糖技术检测癌症),PET实验还可以提供活组织中的生化机制以及信息神经递质和脑受体之间的相互作用的相关信息。在过去的二十年里,大量的放射性药物已用于检测AD患者的影像学病变。tau蛋白聚集和β淀粉样蛋白斑块也可以通过放射性配体而可视化。这一直是最近开发获FDA批准的放射性药物的研究重点。本文旨在总结PET和SPECT对AD病理生理的显像技术的研究进展。
关键词: 淀粉样蛋白,放射性示踪剂,PET,SPECT,tau蛋白。
Current Medicinal Chemistry
Title:PET and SPECT Radiotracers for Alzheimer's Disease
Volume: 22 Issue: 28
Author(s): Killian Oukoloff, Monika Cieslikiewicz-Bouet, Sovy Chao, Emilie Da Costa Branquinho, Cedric Bouteiller, Ludovic Jean, Pierre-Yves Renardq and Pierre-Yves Renard
Affiliation:
关键词: 淀粉样蛋白,放射性示踪剂,PET,SPECT,tau蛋白。
摘要: The two main pathological hallmarks of Alzheimer’s disease (AD) in the brain are senile plaques (SPs) composed of beta-amyloid (Aβ) peptides and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein. These hallmarks are associated with a cholinergic deficit. While the process leading to the development of AD is complex and multifactorial, and the etiology of AD is not completely known, it is nowadays clear that AD is a multifaceted illness requiring the combination of synergetic treatment strategies. Because definite diagnosis is achieved by postmortem examination of the brain, new noninvasive diagnostic imaging modalities for AD are in high demand, both to detect and monitor the evolution of this sickness, and evaluate the efficacy of treatments. Positron Emission Tomography (PET) is a nuclear molecular imaging technique that uses radiopharmaceuticals labeled with a positron-emitting isotope (carbon-11, fluorine-18, copper-64, gallium- 68…), to visualize in vivo cellular metabolism with high-spatial resolution and unique sensitivity, while Single-Photon Emission Computed Tomography (SPECT) using radioisotopes such as technetium-99m or iodine-123. Besides being a powerful tool for diagnosis (mostly in oncology with [18F]-FDG), PET experiments can provide information about biochemical mechanisms in living tissues or interactions between neurotransmitter and brain receptors. For the past two decades, numerous radiopharmaceuticals have been developed for imaging the lesions observed in AD patients. Tau aggregates and Aβ plaques can also be visualized and quantified by mean of specific radioligands. The latter has been the focus of intense research efforts lately, leading to new FDA approved radiopharmaceuticals. This paper aimed at summarizing the recent advances in PET and SPECT imaging of AD pathophysiology.
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Killian Oukoloff, Monika Cieslikiewicz-Bouet, Sovy Chao, Emilie Da Costa Branquinho, Cedric Bouteiller, Ludovic Jean , Pierre-Yves Renardq and Pierre-Yves Renard , PET and SPECT Radiotracers for Alzheimer's Disease, Current Medicinal Chemistry 2015; 22 (28) . https://dx.doi.org/10.2174/0929867322666150805094645
DOI https://dx.doi.org/10.2174/0929867322666150805094645 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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