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

Abstract

The 18-kDa mitochondrial translocator protein (TSPO) is upregulated in high-grade astrocytomas and can be imaged by PET using the selective radiotracer 11 C-(R)PK11195. We investigated 11 C-(R)PK11195 binding in human gliomas and its relationship with TSPO expression in tumor tissue and glioma-associated microglia/macrophages (GAMs) within the tumors. Methods: Twenty-two glioma patients underwent dynamic 11 C-(R)PK11195 PET scans and perfusion MR imaging acquisition. Parametric maps of 11 C-(R)PK11195 binding potential (BP ND ) were generated. Coregistered MR/PET images were used to guide tumor biopsy. The tumor tissue was quantitatively assessed for TSPO expression and infiltration of GAMs using immunohistochemistry and double immunofluorescence. The imaging and histopathologic parameters were compared among different histotypes and grades and correlated with each other. Results: BP ND of 11 C-(R)PK11195 in high-grade gliomas was 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 BP ND in the tumors. GAMs only partially contributed to the overall TSPO expression within the tumors, and TSPO expression in GAMs did not correlate with tumor BP ND . Conclusion: PET with 11 C-(R)PK11195 in human gliomas predominantly reflects TSPO expression in tumor cells. It therefore has the potential to effectively stratify patients who are suitable for TSPO-targeted treatment.

The 18-kDa mitochondrial translocator protein in gliomas: from the bench to bedside

“…Secondly, we characterized gliomas of different grade using [ 11 C]-(R)PK11195 PET-imaging, compared structural MRI and rCBV maps with PET imaging and validated findings with analysis of the tumour tissue [25]. Our results proved that [ 11 C]-(R)PK11195 PET-imaging can be used to stratify patients for TSPO targeted treatment and that such treatment would predominantly challenge neoplastic cells.…”

TSPO Imaging in Glioblastoma Multiforme: A Direct Comparison Between 123I-CLINDE SPECT, 18F-FET PET, and Gadolinium-Enhanced MR Imaging

“…Increased 18 F-FET uptake has been documented experimentally and clinically in reactive astrogliosis secondary to infection, ischemia, radiation injury, demyelination, and hematoma, indicating that 18 F-FET is not entirely glioma-specific (4-7). In contrast, no TSPO expression was found in reactive astrogliosis in a recent study in untreated human glioma patients (17). In addition to binding to glioma cells, TSPO tracers bind to myeloid cell lines, including glioma-associated microglia and macrophages (18).…”

“…This study follows 4 previous studies demonstrating TSPO in 1-3 patients with GBM using the TSPO PET tracer 11 C-PK11195 PET (14)(15)(16)(17). To our knowledge, this is the first study to address the clinical value of TSPO imaging in GBM patients by comparing the second-generation TSPO SPECT tracer 123 I-CLINDE with 18 F-FET PET and contrast-enhanced structural imaging.…”

“…Thus, the addition of TSPO imaging to 18 F-FET PET has the potential to add information about areas of very active tumor cell proliferation in GBM. This may explain why low-grade gliomas have few or no TSPO binding sites (17).…”

PET for Therapy Response Assessment in Glioblastoma

“…Another interesting new PET target is the translocator protein (TSPO), a mitochondrial membrane protein highly expressed in activated microglia, macrophages, and neoplastic cells. Imaging with the TSPO ligand 11 C-(R)PK11195 demonstrates increased binding in HGG compared to low-grade gliomas and normal brain parenchyma (123,124). More recently, the TSPO ligand 18 F-DPA-714 has been evaluated in glioma animal models, but results in human glioma patients are pending (31,125,126).…”