Longitudinal assessment of cerebral β-Amyloid deposition in mice overexpressing Swedish mutant β-Amyloid precursor protein using 18F-florbetaben PET

Free to read The progression of β-amyloid deposition in the brains of mice overexpressing Swedish mutant β-amyloid precursor protein (APP-Swe), a model of Alzheimer disease (AD), was investigated in a longitudinal PET study using the novel β-amyloid tracer 18 F-florbetaben. Methods: Groups of APP-Swe and age-matched wild-type (WT) mice (age range, 10–20 mo) were investigated. Dynamic emission recordings were acquired with a small-animal PET scanner during 90 min after the administration of 18 F-florbetaben (9 MBq, intravenously). After spatial normalization of individual PET recordings to common coordinates for mouse brain, binding potentials (BP ND ) and standardized uptake value ratios (SUVRs) were calculated relative to the cerebellum. Voxelwise analyses were performed using statistical parametric mapping (SPM). Histochemical analyses and ex vivo autoradiography were ultimately performed in a subset of animals as a gold standard assessment of β-amyloid plaque load. Results: SUVRs calculated from static recordings during the interval of 30–60 min after tracer injection correlated highly with estimates of BP ND based on the entire dynamic emission recordings. 18 F-florbetaben binding did not significantly differ in APP-Swe mice and WT animals at 10 and 13 mo of age. At 16 mo of age, the APP-Swe mice had a significant 7.9% increase ( P 18 F-florbetaben uptake above baseline and at 20 mo there was a 16.6% increase ( P P R = 0.95, P < 0.001). Conclusion: In the first longitudinal PET study in an AD mouse model using the novel β-amyloid tracer 18 F-florbetaben, the temporal and spatial progression of amyloidogenesis in the brain of APP-Swe mice were sensitively monitored. This method should afford the means for preclinical testing of novel therapeutic approaches to the treatment of AD.