Molecular imaging of glial activation in the GFAP-IL6 chronic inflammation mouse model with TSPO radioligand 18F-PBR111

Chronic neuroinflammation plays a central role in the development and progression of numerous neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and Huntington’s diseases. Non-invasive imaging approaches capable of tracking neuroinflammatory processes over time are essential for elucidating disease mechanisms and evaluating emerging therapies. Among these, positron emission tomography (PET) using translocator protein (TSPO) ligands has emerged as a powerful tool to visualize glial activation in vivo. In this study, we assessed the potential of the TSPO radioligand 18F-PBR111 for imaging neuroinflammation in the GFAP-IL6 transgenic mouse model, which chronically overexpresses interleukin-6 (IL-6) under the astrocyte-specific GFAP promoter. Dynamic PET/CT imaging was performed in GFAP-IL6 and age-matched C57BL/6 wild-type mice, followed by ex vivo validation using immunohistochemistry and autoradiography. We observed a two-fold increase in cerebellar 18F-PBR111 uptake in GFAP-IL6 mice, alongside elevated binding of the alternative TSPO ligand 125I-CLINDE. Immunostaining confirmed increased TSPO and Iba1 expression, with clear co-localization indicating activated microglia. These results demonstrate a strong correlation between the in vivo PET signal and underlying microglial activation. Our findings validate 18F-PBR111 as a reliable biomarker for chronic neuroinflammation in a model characterized by astrocyte-driven IL-6 overexpression. This work underscores the utility of TSPO-targeted PET imaging for longitudinal monitoring and therapeutic evaluation in neuroinflammatory conditions and supports its use in translational research targeting glial activation.