PET imaging of translocator protein (18 kDa) in a mouse model of Alzheimer's disease using N-(2,5-dimethoxybenzyl)-2-18F-fluoro-N-(2-phenoxyphenyl)acetamide

Abstract

Herein we aimed to evaluate the utility of N-(2,5-dimethoxybenzyl)- 2-18F-fluoro-N-(2-phenoxyphenyl)acetamide (18F-PBR06) for detecting alterations in translocator protein (TSPO) (18 kDa), a biomarker of microglial activation, in a mouse model of Alzheimer's disease (AD). Methods: Wild-type (wt) and AD mice (i.e., APPL/S) underwent 18FPBR06 PET imaging at predetermined time points between the ages of 5-6 and 15-16 mo. MR images were fused with PET/CT data to quantify 18F-PBR06 uptake in the hippocampus and cortex. Ex vivo autoradiography and TSPO/CD68 immunostaining were also performed using brain tissue from these mice. Results: PET images showed significantly higher accumulation of 18F-PBR06 in the cortex and hippocampus of 15- to 16-mo-old APPL/S mice than agematched 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 although no significant difference was found between wt and APPL/S mice aged 9-10 mo or less using PET (P 5 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- to 16-mo-old mice correlated well with autoradiography and immunostaining (i.e., increased 18F-PBR06 uptake in brain regions containing elevated CD68 and TSPO staining in APPL/S mice, compared with wts). Conclusion: 18F-PBR06 shows great potential as a tool for visualizing TSPO/microglia in the progression and treatment of AD.