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

Research output: Contribution to journalArticle

  • External authors:
  • Zhangjie Su
  • Pascal F Durrenberger
  • Konstantina Karabatsou
  • Gerard Thompson
  • Federico E Turkheimer
  • Karolina Janczar
  • Daniel DuPlessis
  • Andrew Brodbelt
  • Karl Herholz

Abstract

Introduction: 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 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 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 gliomas predominantly reflects TSPO expression in tumor cells. It therefore has the potential to effectively stratify patients that are suitable for TSPO targeted treatment.

Bibliographical metadata

Original languageEnglish
Article numberJNUMED/2014/151621
Pages (from-to)512-7
Number of pages504
JournalThe journal of Nuclear Medicine
Volume56
Issue number4
DOIs
Publication statusPublished - Apr 2015

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