Abstract
Herein we aim to evaluate the utility of 18F-PBR06 for detecting alterations in translocator protein 18 kDa (TSPO), a biomarker of microglial activation, in a mouse model of Alzheimer’s disease (AD). Methods: Wild-type (wt) and AD mice (i.e., Thy1-hAPPLond/Swe (APPL/S)) underwent 18F-PBR06-PET imaging at predetermined time-points between the ages of 5-6 and 15-16 months. MR images were fused with PET/CT data to quantify 18F-PBR06 uptake in hippocampus and cortex. ex vivo autoradiography and TSPO/CD68 immunostaining was also performed using brain tissue from these mice. Results: PET images showed significantly higher accumulation of 18F-PBR06 in cortex/hippocampus of 15-16 month old APPL/S mice compared to age-matched wts (cortex/muscle: 2.43 ± 0.19 vs 1.55 ± 0.15, P < 0.005; hippocampus/muscle: 2.41 ± 0.13 vs 1.55 ± 0.12, P < 0.005). And while no significant difference was found between wt and APPL/S mice aged ≤9-10 months using PET (P = 0.64), we were able to visualize and quantify a significant difference in 18F-PBR06 uptake in these mice using autoradiography (cortex/striatum: 1.13 ± 0.04 vs 0.96 ± 0.01, P < 0.05; hippocampus/striatum: 1.266 ± 0.003 vs 1.096 ± 0.017, P < 0.001). PET results for 15-16 month old mice correlated well with autoradiography and immunostaining – i.e., increased 18F-PBR06 uptake in brain regions containing elevated CD68, a marker of microglial activation, and TSPO staining in APPL/S mice compared to wts. Conclusion: 18F-PBR06 shows great potential as a tool for visualizing TSPO/microglia in the progression and treatment of AD.
- Animal Imaging
- Molecular Imaging
- Neurology
- Alzheimers disease
- Microglial activation
- positron emission tomography
- translocator protein 18 kDa
- Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.