Hyperpolarized 13C-glucose magnetic resonance highlights reduced aerobic glycolysis in vivo in infiltrative glioblastoma

Sci Rep. 2021 Mar 11;11(1):5771. doi: 10.1038/s41598-021-85339-7.

Abstract

Glioblastoma (GBM) is the most aggressive brain tumor type in adults. GBM is heterogeneous, with a compact core lesion surrounded by an invasive tumor front. This front is highly relevant for tumor recurrence but is generally non-detectable using standard imaging techniques. Recent studies demonstrated distinct metabolic profiles of the invasive phenotype in GBM. Magnetic resonance (MR) of hyperpolarized 13C-labeled probes is a rapidly advancing field that provides real-time metabolic information. Here, we applied hyperpolarized 13C-glucose MR to mouse GBM models. Compared to controls, the amount of lactate produced from hyperpolarized glucose was higher in the compact GBM model, consistent with the accepted "Warburg effect". However, the opposite response was observed in models reflecting the invasive zone, with less lactate produced than in controls, implying a reduction in aerobic glycolysis. These striking differences could be used to map the metabolic heterogeneity in GBM and to visualize the infiltrative front of GBM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerobiosis
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / metabolism*
  • Carbon Isotopes / chemistry*
  • Cell Line, Tumor
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / metabolism*
  • Glucose / metabolism*
  • Glycolysis*
  • Humans
  • Lactic Acid / metabolism
  • Magnetic Resonance Imaging*
  • Metabolomics
  • Mice
  • Mice, SCID
  • Pyruvic Acid / metabolism

Substances

  • Carbon Isotopes
  • Aspartic Acid
  • Lactic Acid
  • Pyruvic Acid
  • N-acetylaspartate
  • Carbon-13
  • Glucose