Krishnadas Natasha, Villemagne Victor L, Doré Vincent, Rowe Christopher C
Florey Department of Neurosciences and Mental Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria, Australia; Department of Molecular Imaging & Therapy, Austin Health, Victoria, Australia.
Department of Molecular Imaging & Therapy, Austin Health, Victoria, Australia.
Semin Nucl Med. 2021 May;51(3):241-252. doi: 10.1053/j.semnuclmed.2020.12.005. Epub 2021 Jan 19.
Amyloid-β (Aβ) PET imaging has now been available for over 15 years. The ability to detect Aβ in vivo has greatly improved the clinical and research landscape of Alzheimer's disease (AD) and other neurodegenerative conditions. Aβ imaging provides very reliable, accurate, and reproducible measurements of regional and global Aβ burden in the brain. It has proved invaluable in anti-Aβ therapy trials, and is now recognized as a powerful diagnostic tool. The appropriate use of Aβ PET, when combined with comprehensive clinical evaluation by a dementia-trained specialist, can improve the accuracy of a clinical diagnosis of AD and substantially alter management. It can assist in differentiating AD from other neurodegenerative conditions, often by its ability to rule out the presence of Aβ. When combined with tau imaging, further increase in specificity for the diagnosis of AD can be achieved. The integration of Aβ PET, in conjunction with biomarkers of tau, neurodegeneration and neuroinflammation, into large, longitudinal, observational cohort studies continues to increase our understanding of the development of AD. Its incorporation into clinical trials has been pivotal in defining the most effective anti-Aβ biological therapies and optimal dosing so that effective disease modifying therapy now appears imminent. Aβ deposition is a gradual and protracted process, permitting a wide treatment window for anti-Aβ therapies and Aβ PET has made trials in this preclinical AD period feasible. Continuing improvement in Aβ tracer target to background ratio is allowing trials in earlier AD that tailor drug dosage to Aβ level. The quest to standardize quantification and define universally applicable thresholds for all Aβ tracers has produced the Centiloid method. Centiloid values that correlate well with neuropathologic findings and prognosis have been identified. Rapid cloud-based automated individual scan analysis is now possible and does not require MRI. Challenges remain, particularly around cross camera standardized uptake value ratio variation that need to be addressed. This review will compare available Aβ radiotracers, discuss approaches to quantification, as well as the clinical and research applications of Aβ PET.
淀粉样蛋白β（Aβ）正电子发射断层扫描（PET）成像现已应用超过15年。体内检测Aβ的能力极大地改善了阿尔茨海默病（AD）和其他神经退行性疾病的临床和研究格局。Aβ成像能够非常可靠、准确且可重复地测量大脑区域和整体的Aβ负荷。它在抗Aβ治疗试验中已证明具有极高价值，如今被公认为一种强大的诊断工具。当与经过痴呆症培训的专家进行的全面临床评估相结合时，合理使用Aβ PET能够提高AD临床诊断的准确性，并显著改变治疗管理方式。它通常能够通过排除Aβ的存在，协助将AD与其他神经退行性疾病区分开来。与tau成像相结合时，可进一步提高AD诊断的特异性。将Aβ PET与tau、神经退行性变和神经炎症的生物标志物整合到大型纵向观察队列研究中，不断加深我们对AD发病机制的理解。将其纳入临床试验对于确定最有效的抗Aβ生物疗法和最佳剂量至关重要，因此有效的疾病修饰疗法似乎即将出现。Aβ沉积是一个渐进且漫长的过程，为抗Aβ疗法提供了广阔的治疗窗口，而Aβ PET使在这个临床前AD阶段进行试验成为可能。Aβ示踪剂靶本底比的持续改善使得在更早的AD阶段进行试验成为可能，这些试验可根据Aβ水平调整药物剂量。为所有Aβ示踪剂标准化定量并定义普遍适用阈值的探索产生了百分位法。已确定与神经病理学发现和预后密切相关的百分位数值。现在可以进行基于云的快速自动化个体扫描分析，且无需磁共振成像（MRI）。挑战依然存在，尤其是围绕不同相机间标准化摄取值比的差异，这需要加以解决。本综述将比较现有的Aβ放射性示踪剂，讨论定量方法以及Aβ PET的临床和研究应用。
