The 18-kDa Mitochondrial Translocator Protein in Human Gliomas: A 11C-(R)PK11195 PET Imaging and Neuropathology Study.
Creators
- 1. Wolfson Molecular Imaging Center, University of Manchester, UK
- 2. Division of Brain Science, Imperial College London, UK
- 3. Wolfson Molecular Imaging Center, University of Manchester, UK and Department of Neurosurgery, Salford Royal NHS Foundation Trust, UK
- 4. Department of Neurosurgery, Salford Royal NHS Foundation Trust, UK
- 5. Center for Neuroimaging, Institute of Psychiatry, King's College London, UK
- 6. Neuropathology Unit, Salford Royal NHS Foundation Trust, UK
- 7. Department of Neurosurgery, The Walton Center NHS Foundation Trust, UK
Description
The 18-kDa mitochondrial translocator protein (TSPO) is up-regulated in high grade astrocytomas and can be imaged by positron emission tomography (PET) using the selective radiotracer 11C-(R)PK11195. We investigated 11C-(R)PK11195 binding in human gliomas and its relationship with TSPO expression in tumor tissue and glioma associated microglia/macrophages within the tumors.
METHODS: Twenty-two glioma patients 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 glioma associated microglia/macrophages (GAMs) 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 gliomas were significantly higher than in low-grade astrocytomas and low-grade oligodendrogliomas. TSPO in gliomas was expressed predominantly by neoplastic cells, and its expression correlated positively with BPND in the tumors. Glioma associated microglia/macrophages only partially contributed to the overall TSPO expression within the tumors, and TSPO expression in GAMs did not correlate with tumor BPND.
CONCLUSION: PET with 11C-(R)PK11195 in human gliomas predominantly reflects TSPO expression in tumor cells. It therefore has the potential to effectively stratify patients that are suitable for TSPO targeted treatment.
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