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

The deposition of fi-amyloid (Afi) 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 Afi plaques in the AD brain using PET imaging. After a set of comprehensive preclinical assessments, we screened out a promising Afi-PET tracer, [18F]92, with a high binding affinity to the Afi aggregates, significant binding ability with the AD brain sections, and optimal brain pharmacokinetic properties in rodents and non-human primates. The first -inhuman PET study declared that [18F]92 displayed low white matter uptake and could bind to Afi pathology for distinguishing AD from healthy control subjects. All these results support that [18F]92 might become a promising PET tracer for visualizing Afi pathology in AD patients.

Automated summary

We have discovered and developed a class of diaryl-azine derivatives for detecting Afi plaques in the AD brain using PET imaging. After comprehensive assessments, we identified a promising Afi-PET tracer, [18F]92, with high binding affinity to Afi aggregates, significant binding ability with AD brain sections, and optimal brain pharmacokinetic properties. The first in-human PET study showed that [18F]92 displayed low white matter uptake and could bind to Afi pathology for distinguishing AD from healthy controls, making it a promising PET tracer for visualizing Afi pathology in AD patients.