[18F]-florzolotau PET imaging in Alzheimer's disease: Current evidence and future directions

Abstract

Tau positron emission tomography (PET) has become a central imaging modality for in vivo detection and quantification of tau pathology across the Alzheimer's disease (AD) clinical and biological continuum. [18F]-Florzolotau is a second-generation tau PET tracer developed to improve target-to-background contrast and mitigate off-target binding relative to first-generation ligands, thereby improving interpretability for translational research and clinical use. In this narrative review, we provide a critical appraisal of the available literature on [18F]-Florzolotau PET imaging in AD, with emphasis on diagnostic and differential-diagnostic performance, the spatiotemporal topography of tau deposition in relation to Braak staging and disease progression, and the clinical significance of tracer uptake with respect to cognitive measures, disease severity, and prognosis. Eligible studies were clinical investigations published between 2020 and 2025 that applied [18F]-Florzolotau PET in cohorts spanning cognitively unimpaired individuals through symptomatic AD stages. Across reports, [18F]-Florzolotau PET differentiated AD dementia from cognitively unimpaired comparators with high accuracy, with sensitivities ≥ 90% and specificities of 87–96%. Regional uptake patterns were broadly consistent with Braak-like propagation, progressing from medial temporal regions toward associative neocortex in parallel with increasing clinical severity. Quantitative tracer uptake also correlated with global cognition and key domains, including episodic memory and executive function. We conclude that [18F]-Florzolotau PET provides a robust in vivo measure of AD tau burden, motivating further evaluation for diagnostic and prognostic applications. Larger multicenter studies with harmonized acquisition/quantification and head-to-head comparisons versus other second-generation tracers remain priorities.