Fluorine-18-Labeled Diaryl-azines as Improved β-Amyloid Imaging Tracers: From Bench to First-in-Human Studies

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, [¹⁸F]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 [¹⁸F]92 displayed low white matter uptake and could bind to Aβ pathology for distinguishing AD from healthy control subjects. All these results support that [¹⁸F]92 might become a promising PET tracer for visualizing Aβ pathology in AD patients.