Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA.
Department of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA.
Clin Nucl Med. 2023 Aug 1;48(8):689-691. doi: 10.1097/RLU.0000000000004710. Epub 2023 May 23.
Passive immunotherapy for Alzheimer disease has been tried for over 10 years without success. However, in 2021 and most recently in January 2023, the US Food and Drug Administration granted accelerated approval of 2 antibodies for this purpose, aducanumab and lecanemab. In both cases, the approval was based on a presumed therapy-related removal of amyloid deposits from the brain and, in the case of lecanemab, also some delay in cognitive decline. We question the validity of the evidence for the removal of amyloid in particular as assessed by amyloid PET imaging, believing that what is observed is more likely a large nonspecific amyloid PET signal in the white matter that diminishes during immunotherapy-in line with dose-dependent increases in amyloid-related imaging abnormalities and increased loss of cerebral volume in treated compared with placebo patients. To investigate this further, we recommend repeat FDG PET and MRI in all future immunotherapy trials.
针对阿尔茨海默病的被动免疫疗法已经尝试了 10 多年，但并未取得成功。然而，在 2021 年和最近的 2023 年 1 月，美国食品和药物管理局为此目的加速批准了 2 种抗体，即 aducanumab 和 lecanemab。在这两种情况下，批准的依据是假定治疗相关的大脑中淀粉样蛋白沉积的清除，而对于 lecanemab，也有一些认知能力下降的延迟。我们质疑特别是通过淀粉样蛋白 PET 成像评估的淀粉样蛋白清除的证据的有效性，认为观察到的更可能是免疫治疗过程中大脑白质中大量非特异性淀粉样蛋白 PET 信号的减少，这与治疗组与安慰剂组相比，淀粉样蛋白相关成像异常增加和脑容量减少呈剂量依赖性增加相一致。为了进一步研究这一点，我们建议在所有未来的免疫治疗试验中重复进行 FDG PET 和 MRI。
