Preclinical head-to-head comparison of SV2A-PET with FDG-PET and structural MRI in a tau mouse model

Ziel/Aim Transgenic mice with overexpression of tau can serve to study neuronal injury. Novel positron emission tomography (PET) tracers for SV2A assessment as a surrogate of synaptic density facilitate detection of neuronal injury in vivo, along with established imaging biomarkers such as FDG-PET and atrophy in magnetic resonance imaging (MRI). We aimed to perform a head to head comparison of SV2A-PET, FDG-PET and structural MRI as biomarkers for neuronal injury in a tau mouse model.

Methodik/Methods 7 P301 S and 7 C57BL/6 mice aged 5 to 6 months were imaged by 18-F-UCB-H SV2A-PET (0–90 min p.i.) and FDG-PET (30–60 min p.i.) at a Siemens Inveon PET system. Additional FDG-PET/MRI was performed at Mediso 3 T system. Standardized uptake value ratios (SUVr) images for both PET ligands were calculated (30–60 min p.i. frame) by normalization to global mean. Neocortex, hippocampus and brainstem served as target regions. Effect sizes (Cohen’s d) were calculated for the contrast of P301 S versus WT and compared between biomarkers.

Ergebnisse/Results FDG-PET revealed congruent mild to moderate hypometabolism in P301 S mice in contrast to WT when compared between both PET machines. SV2A-PET SUVr quantification showed higher effect sizes for the hippocampus (d = 0.74 vs. 0.45) but lower effect sizes for the neocortex (d = 0.31 vs. 0.51) and the brainstem (d = 0.21 vs. 1.11) when compared to FDG-PET. MRI analyses are ongoing.

Schlussfolgerungen/Conclusions Preliminary data suggests that SV2A imaging in P301 S mice might have an advantage for detection of neuronal injury in the hippocampus of this tau mouse model, whereas FDG-PET tended to be superior in the neocortex and brainstem. Different quantification approaches including kinetic modelling need to be evaluated for validation of these data.