Screening of [F]Florbetazine for Aβ Plaques and a Head-to-Head Comparison Study with [C]Pittsburgh Compound-B ([C]PiB) in Human Subjects.

Positron emission tomography (PET) imaging of amyloid-β (Aβ) has emerged as a crucial strategy for early diagnosis and monitoring of therapeutic advancements targeting Aβ. In our previous first-in-human study, we identified that [F]Florbetazine ([F]), featuring a diaryl-azine scaffold, exhibits higher cortical uptake in Alzheimer's disease (AD) patients compared to healthy controls (HC). Building upon these promising findings, this study aimed to characterize the diagnostic potential of [F] and its dimethylamino-modified tracer [F] and further compare them with the benchmark [C]PiB in the same cohort of AD patients and age-matched HC subjects. The cortical accumulation of these tracers was evident, with no significant radioactivity retention observed in the cortex of HC subjects, consistent with [C]PiB images (correlation coefficient of 0.9125 and 0.7883 between [F]Florbetazine/[F] and [C]PiB, respectively). Additionally, quantified data revealed higher standardized uptake value ratios (SUVR) (with the cerebellum as the reference region) of [F]Florbetazine/[F] in AD patients compared to the HC group ([F]Florbetazine: 1.49 vs 1.16; [F]: 1.33 vs 1.20). Notably, [F]Florbetazine exhibited less nonspecific bindings in myelin-rich regions, compared to the dimethylamino-substituted [F], akin to [C]PiB. Overall, this study suggests that [F]Florbetazine displays superior characteristics to [F] in identifying Aβ pathology in AD. Furthermore, the close agreement between the uptakes in nontarget regions for [F]Florbetazine and [C]PiB in this head-to-head comparison study underscores its suitability for both clinical and research applications.