Monitoring brain tumor vascular heamodynamic following anti-angiogenic therapy with advanced magnetic resonance imaging in mice

PLoS One. 2014 Dec 15;9(12):e115093. doi: 10.1371/journal.pone.0115093. eCollection 2014.

Abstract

Advanced MR imaging methods have an essential role in classification, grading, follow-up and therapeutic management in patients with brain tumors. With the introduction of new therapeutic options, the challenge for better tissue characterization and diagnosis increase, calling for new reliable non-invasive imaging methods. In the current study we evaluated the added value of a combined protocol of blood oxygen level dependent (BOLD) imaging during hyperoxic challenge (termed hemodynamic response imaging (HRI)) in an orthotopic mouse model for glioblastoma under anti-angiogenic treatment with B20-4.1.1, an anti-VEGF antibody. In glioblastoma tumors, the elevated HRI indicated progressive angiogenesis as further confirmed by histology. In the current glioblastoma model, B20-treatment caused delayed tumor progression with no significant changes in HRI yet with slightly reduced tumor vascularity as indicated by histology. Furthermore, fewer apoptotic cells and higher proliferation index were detected in the B20-treated tumors compared to control-treated tumors. In conclusion, HRI provides an easy, safe and contrast agent free method for the assessment of the brain hemodynamic function, an additionally important clinical information.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology
  • Contrast Media
  • Disease Models, Animal
  • Glioblastoma / blood supply*
  • Glioblastoma / drug therapy
  • Glioblastoma / pathology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Neovascularization, Pathologic
  • Neurovascular Coupling / immunology
  • Vascular Endothelial Growth Factors / antagonists & inhibitors
  • Vascular Endothelial Growth Factors / immunology

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Contrast Media
  • Vascular Endothelial Growth Factors