RT Journal Article SR Electronic T1 Dynamically Monitor Neuroinflammation in a Mouse Model of Mo/Hu APPswePS1dE9 Mice with [18F]-DPA714 PET Imaging JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1229 OP 1229 VO 59 IS supplement 1 A1 Wei, Hu A1 Jun, Zhao A1 Min, Yang A1 Ya-Lin, Wang A1 Wei-Qi, Bao A1 Dong-Hui, Pan YR 2018 UL http://jnm.snmjournals.org/content/59/supplement_1/1229.abstract AB 1229Objectives: Neuroinflammation is a pathological hallmark of Alzheimer’s disease (AD) and it is well established that microglia play a core role in the pathologies of AD. In order to monitor microglia activation and neuroinflammation, we performed PET imaging in the B6.Cg-Tg (APPswe, PSEN1dE9)85Dbo/Mmjax (Mo/Hu APPswePS1dE9) mouse model using 18F-labeled DPA-714, a radio-ligand of the 18-kDa translocator protein (TSPO). Methods: We prepared [18F]-DPA714 and optimized [18F]-fluorination condition for a high radiochemical yield. Wild-type (Wt) and Mo/Hu APPswePS1dE9 mice underwent respectively [18F]-DPA714 PET scanning at the ages of 6-7, 9-10,12-13 and 15-16 months. In addition, blocking experiment was performed with PK11195 (1 mg/kg) at the age of 12-13 months. Brain PET images were reconstructed using OSEM 2D algorithm with no attenuation correction. These images were then co-registered to a MRI template atlas in PMOD 3.7. Hippocampus and cortex region of interest (ROI) were determined based on the standard regions of interest extracted from this MRI template atlas. Immunofluorescence staining was carried out to characterize the microdistribution of [18F]-DPA714 in the brain tissues of 15- to 16-mo-old Mo/Hu APPswePS1dE9 and Wt mice. Results: The optimal radiochemical yield of 42.3 ± 5.1 %(non-decay-corrected)for [18F]-DPA714 was obtained in reaction with 2 mg/300ul acetonitrile of precursor at 105°C for 10 min. PET images showed significant higher accumulation of [18F]-DPA714 in the cortex and hippocampus of 12-13 months old Mo/Hu APPswePS1dE9 mice than age-matched Wt (cortex/muscle: 2.77 ±0.13 vs. 1.93 ±0.32, p=0.0014; hippocampus/muscle:3.33 ± 0.10 vs. 2.10 ± 0.35, p=0.0008) and 15-16 months (cortex/muscle: 2.64 ± 0.14 vs. 1.86 ± 0.52,p=0.0159; hippocampus/muscle:2.89 ± 0.53 vs. 1.77 ± 0.48, p=0.0050). Immunofluorescence staining showed activated microglia and elevated TSPO expression in the cortex and hippocampus of 15- to 16-mo-old Mo/Hu APPswePS1dE9 versus Wt mice. Conclusion: [18F]-DPA714 has great potential in monitoring the neuroinflammation course and therapeutic effect of Alzheimer's disease.