Physiologic MR imaging of the tumor microenvironment revealed switching of metabolic phenotype upon recurrence of glioblastoma in humans

Andreas Stadlbauer, Stefan Oberndorfer, Max Zimmermann, Bertold Renner, Michael Buchfelder, Gertraud Heinz, Arnd Doerfler, Andrea Kleindienst, Karl Roessler

Research output: Journal article (peer-reviewed)Journal article

23 Citations (Scopus)

Abstract

Treating recurrent glioblastoma (GB) is one of the challenges in modern neurooncology. Hypoxia, neovascularization, and energy metabolism are of crucial importance for therapy failure and recurrence. Twenty-one patients with initially untreated GB who developed recurrence were examined with a novel MRI approach for noninvasive visualization of the tumor microenvironment (TME). Imaging biomarker information about oxygen metabolism (mitochondrial oxygen tension) and neovascularization (microvascular density and type) were fused for classification of five different TME compartments: necrosis, hypoxia with/without neovascularization, oxidative phosphorylation, and glycolysis. Volume percentages of these TME compartments were compared between untreated and recurrent GB. At initial diagnosis, all 21 GB showed either the features of a glycolytic dominant phenotype with a high percentage of functional neovasculature (N = 12) or those of a necrotic/hypoxic dominant phenotype with a high percentage of defective tumor neovasculature (N = 9). At recurrence, all 21 GB revealed switching of the initial metabolic phenotype: either from the glycolytic to the necrotic/hypoxic dominant phenotype or vice-versa. A necrotic/hypoxic phenotype at recurrence was associated with a higher rate of multifocality of the recurrent lesions. Our MRI approach may be helpful for a better understanding of treatment-induced metabolic phenotype switching and for future studies developing targeted therapeutic strategies for recurrent GB.

Original languageEnglish
Pages (from-to)528-538
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume40
Issue number3
DOIs
Publication statusPublished - 01 Mar 2020

Keywords

  • Aged
  • Brain Neoplasms/diagnostic imaging
  • Databases, Factual
  • Female
  • Glioblastoma/diagnostic imaging
  • Glycolysis
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local/diagnostic imaging
  • Neovascularization, Pathologic/diagnostic imaging
  • Retrospective Studies
  • Tumor Microenvironment

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