Fluorine-18-Labeled Diaryl-azines as Improved β-Amyloid Imaging Tracers: From Bench to First-in-Human Studies
Yuying Li, Kaixiang Zhou, Xiaojun Zhang, Hailong Zhao, Xiaoming Wang, Ruilin Dong, Yan Wang, Baian Chen, Xiao‐Xin Yan, Jiapei Dai, Yanying Sui, Jinming Zhang, Mengchao Cui
Abstract
The deposition of β-amyloid (Aβ) in the brain is a pathologic hallmark of Alzheimer’s disease (AD), appearing years before the onset of symptoms, and its detection is incorporated into clinical diagnosis. Here, we have discovered and developed a class of diaryl-azine derivatives for detecting Aβ plaques in the AD brain using PET imaging. After a set of comprehensive preclinical assessments, we screened out a promising Aβ-PET tracer, [ 18 F] 92, with a high binding affinity to the Aβ aggregates, significant binding ability with the AD brain sections, and optimal brain pharmacokinetic properties in rodents and non-human primates. The first-in-human PET study declared that [ 18 F] 92 displayed low white matter uptake and could bind to Aβ pathology for distinguishing AD from healthy control subjects. All these results support that [ 18 F] 92 might become a promising PET tracer for visualizing Aβ pathology in AD patients.