Nuklearmedizin - NuclearMedicine · Apr 2026
Perfusion adjustment masks hypermetabolism in FDG-PET imaging of aging wild-type and Alzheimer's disease mouse models
By Lalia M, Wagner S, Prtvar D et al.
OBJECTIVE: FDG-PET quantifies cerebral glucose metabolism using Total Volume of Distribution (V T ) and Standard Uptake value (SUV). The study compares V T s and SUVs in aging wild-type (WT) and APP NL-G-F mice to determine the more sensitive method for detecting age- and amyloid-related changes in cerebral glucose metabolism. This is based on cellular FDG uptake and the cell type-specific contribution to the FDG-PET signal. METHODS: WT (n=99, up to 21 M) and APP NL-G-F mice (n=55, up to 25 M), all divided into three age groups (3-4 M, 9-13 M, 16-25 M; 47% female), underwent a PET scan after a 30MBq FDG injection. Quantification was performed using an image-derived carotid input function as V T and as SUV. Microglia (MG), astrocytes (A), and neurons (N) were isolated from brain samples from individual mice to determine cellular glucose uptake. The cell type-specific PET contribution was calculated using a system of linear equations with three unknowns for three age groups. RESULTS: The SUVs of WTs increased with age and differed significantly between the three age groups (from young to middle-aged:+11% p=0.040; from middle-aged to old:+26% p<0.001), whereas in APP NL-G-F mice, SUVs increased only from young to middle age (+25%, p=0.037). V T s showed no genotype-dependent differences, despite a close correlation with SUVs ( r=0.55; p<0.001 ). At the cellular level, FDG uptake in MG (p=0.046) and A (p=0.003) increased from the young to the old group in WT. In APP NL-G-F mice, microglial FDG uptake increased between the young and old groups (p=0.002), while neuronal uptake decreased (p<0.001). In both genotypes, FDG uptake by MG and A correlated with SUVs (WT: MG r=0.49, p<0.001; A r=0.51, p=0.010; APP NL-G-F : MG r=0.53, p=0.001; A r=0.49, p=0.011), but not with V T s. MG and A contributions predominated in both genotypes across all age groups. CONCLUSIONS: Age- and amyloid-related hypermetabolism in WT and APP NL-G-F mice is explained by cell type-specific contributions to the FDG-PET signal. SUVs capture these changes more precisely than V T s, because increased perfusion corrects for the increase in FDG uptake in V T. Publication History Article published online: 02 April 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany