Assessment of early-phase [ ¹⁸ F]florbetaben images as a proxy for brain metabolism in mouse models of Alzheimer’s disease

[¹⁸F]FDG-PET and β-amyloid-PET are established tools for assessing biomarker status in Alzheimer's disease. In this study, we evaluated the potential of early-phase [¹⁸F]florbetaben (FBB) PET as a functional proxy for [¹⁸F]FDG-PET in preclinical Alzheimer's disease models by examining regional perfusion and glucose metabolism in two transgenic mouse lines. Ninety-two APPPS1 (n = 17), APPSAA (n = 56), and age- and sex-matched wild-type mice (n = 19; 3-12 months, 40% female) underwent static [¹⁸F]FDG-PET (30-60 min p.i.) and dynamic [¹⁸F]FBB-PET (0-60 min p.i.). Standardized uptake values were derived for both [¹⁸F]FDG-PET and [¹⁸F]FBB-PET for the whole brain and 14 Ma-Benveniste-Mirrione atlas regions. We identified the 1-3 min p.i. time window as optimal, yielding the highest concordance with [¹⁸F]FDG (R = 0.53, p < 0.0001) across all regions. Both APPPS1 and APPSAA mice exhibited significant increases in perfusion (both p < 0.0001) and glucose metabolism (APPPS1: p = 0.0028; APPSAA: p < 0.0001) compared to wild-type controls. These findings demonstrate that early-phase [¹⁸F]FBB-PET not only mirrors [¹⁸F]FDG-PET-derived metabolic changes but also enables a single-scan assessment of β-amyloid pathology and brain function, thereby reducing the number of required scans and potentially the number of animals per study, and strengthening the translational value of preclinical PET research.