The 18-kDa Mitochondrial Translocator Protein in Human Gliomas: An 11C-(R)PK11195 PET Imaging and Neuropathology Study

Introduction: The 18-kDa mitochondrial translocator protein(TSPO) is up-regulated in high grade astrocytomasand can be imaged by positron emission tomography (PET) using the selective radiotracer [11C]-(R)PK11195. We investigated [11C]-(R)PK11195 binding in human gliomasand its relationship with TSPO expression in tumor tissue and gliomaassociated microglia/macrophages within the tumors. Methods: Twenty-two gliomapatients underwent dynamic [11C]-(R)PK11195 PET scans and perfusion MRI acquisition. Parametric maps of [11C]-(R)PK11195 binding potential(BPND) were generated. Co-registered MR/PET images were used to guide tumor biopsy. The tumor tissue was quantitatively assessed for TSPO expression and infiltration of gliomaassociated microglia/macrophages using immunohistochemistry and double immunofluorescence. The imaging and histopathologic parameters were compared among different histotypes and grades, and correlated with each other. Results: BPND of [11C]-(R)PK11195 in high-grade gliomaswere significantly higher than in low-grade astrocytomasand low-grade oligodendrogliomas. TSPO in gliomaswas expressed predominantly by neoplastic cells, and its expression correlated positively with BPND in the tumors. Gliomaassociated microglia/macrophages only minimally contributed to the overall TSPO expression within the tumors, and TSPO expression in GAMs did not correlate with tumor BPND. Conclusions: PET with [11C]-(R)PK11195 in human gliomaspredominantly reflects TSPO expression in tumor cells. It therefore has the potential to effectively stratify patients that are suitable for TSPO targeted treatment.