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The translocator protein (TSPO, 18 kDa), also known as the peripheral benzodiazepine receptor (PBR), is mainly localized in the outer mitochondrial membrane of steroid-synthesizing cells of the peripheral and central nervous system. Activated microglia produce a large number of precursors of inflammatory factors, resulting in the occurrence of neurodegenerative diseases ( Politis et al., 2012 Li et al., 2014). Microglia activated by Aβ depositions is one of the main mechanisms of neuroinflammation. In recent years, it has been found that microglia play a major role in the pathogenesis of AD, which is also currently a hot topic in the study of neurodegenerative diseases. Immunofluorescence staining showed that the activation of microglia and the level of TSPO expression in the cortex and hippocampus of APP/PS1 mice were significantly higher than Wt mice.Ĭonclusion: DPA714, a molecular probe for targeting TSPO, showed great potential in monitoring microglia activation and neuroinflammation, which can be helpful in discovering the best time point for anti-inflammatory therapy in AD.Īlzheimer's disease (AD) is the chronic inflammation of the central nervous system (CNS), including focal brain injury and a lot of beta-amyloid protein (A beta, Aβ) deposition ( Golde, 2016). The same significant difference was found between 15- and 16-months-old APP/PS1 mice (cortex/muscle: 2.64 ± 0.14 vs. Quantitative analysis of brain PET images showed that the DPA714 uptake in the cortex and hippocampus of 12–13-months-old APP/PS1 mice was higher than that of the control mice of the same age (cortex/muscle: 2.77 ± 0.13 vs. Results: Through the reaction of 18F, with 2 mg precursor dissolved in 300 ul acetonitrile at 105☌ for 10 min, we obtained the optimal radiochemical yield of 42.3 ± 5.1% (non-decay correction). The distribution of DPA714 in the brain tissues of 15–16-months-old APP/PS1 and Wt mice were studied by immunofluorescence staining. Reconstructed brain PET images, fused with the Magnetic Resonance Imaging (MRI) template atlas, and the volumes of interests (VOIs) of the hippocampus and cortex were determined. Referring to the DPA714 concentrated situation in the brain, we performed blocking experiments with PK11195 (1 mg/kg) in 12–13-months-old APP/PS1 mice to confirm the specificity of DPA714 for TSPO in the APP/PS1 mice. The same experiments were conducted in Wild-type (Wt) mice as a control. We performed DPA714 PET scanning on APP/PS1 mice at 6–7, 9–10, 12–13, and 15–16 months of age, respectively. To obtain a higher radiochemical yield, we improved the -fluorination conditions in the precursor dosage, reaction temperature, and synthesis time. Methods: We prepared DPA714 and tested the biological characteristics of the molecular probe in normal mice. Motivated by this, Positron emission tomography (PET) imaging in an APP/PS1 mouse model of AD, using 18F-labeled DPA-714 to monitor microglia activation and neuroinflammation, were performed in this paper. Dynamic monitoring neuroinflammation is crucial for discovering the best time point of anti-inflammatory therapy.
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Molecular imaging of neuroinflammatory targeting microglia activation and the high expression of 18-kDa translocator protein (TSPO) has become a hot topic of research in recent years. 5Department of Nuclear Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Chinaīackground: In the pathogenesis of Alzheimer's disease (AD), microglia play an increasingly important role.4State Key Lab of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.3Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Ministry of Health, Wuxi, China.
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