Metabolic response of glioblastoma to superselective intra-arterial cerebral infusion of bevacizumab: a proton MR spectroscopic imaging study

AJNR Am J Neuroradiol. 2012 Dec;33(11):2095-102. doi: 10.3174/ajnr.A3091. Epub 2012 May 10.

Abstract

Background and purpose: SIACI of bevacizumab has emerged as a promising novel therapy in the treatment of recurrent GB. This study assessed the potential of (1)H-MRS as an adjunctive technique in detecting metabolic changes reflective of antiproliferative effects of targeted infusion of bevacizumab in the treatment of GB.

Materials and methods: Eighteen patients enrolled in a phase I/II study of SIACI of bevacizumab for treatment of recurrent GB were included. Concurrent MR imaging and (1)H-MRS scans were performed before and after treatment. Five distinct morphologic ROIs were evaluated for structural and metabolic changes on MR imaging and (1)H-MRS, which included enhancing, nonenhancing T2 hyperintense signal abnormality, and multiple control regions. Pre- and post-SIACI of bevacizumab peak areas for NAA, tCho, tCr, as well as tCho/tCr and tCho/NAA ratios, were derived for all 5 ROIs and compared using the Wilcoxon signed-rank test.

Results: A significant median decrease of 25.99% (range -55.76 to 123.94; P = .006) in tCho/NAA was found post-SIACI of bevacizumab relative to pretreatment values in regions of enhancing disease. A trend-level significant median decrease of 6.45% (range -23.71 to 37.67; P = .06) was noted in tCho/NAA posttreatment in regions of nonenhancing T2-hyperintense signal abnormality.

Conclusions: The results of this (1)H-MRS analysis suggest that GB treatment with SIACI of bevacizumab may be associated with a direct antiproliferative effect, as demonstrated by significant reductions of tCho/NAA after the intervention.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase III
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Bevacizumab
  • Brain / drug effects
  • Brain / metabolism
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism*
  • Cerebral Arteries
  • Choline / metabolism
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism*
  • Humans
  • Infusions, Intra-Arterial
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Protons
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Protons
  • Bevacizumab
  • Aspartic Acid
  • N-acetylaspartate
  • Choline