Abstract
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Objectives The 18kDa translocator protein (TSPO) is highly expressed on the outer membrane of the mitochondria in reactive astrocytes and activated microglia, and proposed as a biomarker of neuroinflammation. The purpose of this study was to evaluate the peritumoral inflammatory reaction in glioma model mouse using TSPO tracer 18F-DPA-714 by small-animal PET/CT.
Methods C57BL/6 male mice (n=5) were stereotactically inoculated in the right hemisphere with murine glioma GL261 cells which did not show significant expression of TSPO. T2-weighted MR images were acquired to monitor tumor growth in vivo until the tumor reached a diameter of 3 mm. Static 10-min PET acquisitions were started 20 minutes after the venous injection of 118F-DPA-714 under isoflurane anesthesia. Ex vivo histological and immunofluorescence staining of brain tissue were performed to confirm the glial activation and compared to the PET imaging.
Results Inoculated tumor showed high intensity on T2-weighted images. PET images showed moderate uptake along the periphery of tumor implantation (the lesion to cerebellum radioactivity ratio = 2.1±0.6). Immunohistochemistry revealed numerous TSPO positive cells in the increased uptake area on PET. These cells were co-localized with CD11b-positive microglia and partially glial fibrillary acidic protein positive astrocytes.
Conclusions Our results revealed increased uptake of 18F-DPA-714 in the vicinity of the tumor. Neuroinflammation represented by microglial activation occurred in peritumoral tissue.