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

J Cereb Blood Flow Metab. 2020 Mar;40(3):528-538. doi: 10.1177/0271678X19827885. Epub 2019 Feb 7.

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.

Keywords: Glioblastoma; angiogenesis; hypoxia; recurrence; treatment failure; tumor microenvironment.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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