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Decrease in tumor cell oxygen consumption after treatment with vandetanib (ZACTIMA; ZD6474) and its effect on

Réginald Ansiaux1, Julie Dewever, Vincent Grégoire

  • 1Biomedical Magnetic Resonance Unit, Louvain Drug Research Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium.

Radiation Research
|November 4, 2009
PubMed

Insights

Vandetanib, a VEGFR inhibitor, increases tumor oxygenation by reducing cellular oxygen consumption. This enhanced oxygenation potentiates radiotherapy effects, suggesting optimized treatment sequencing for cancer therapy.

Area of Science:

  • Oncology
  • Pharmacology
  • Radiotherapy

Background:

  • Vascular Endothelial Growth Factor (VEGF) signaling promotes tumor angiogenesis and hypoxia.
  • VEGF inhibitors are investigated for cancer therapy, but their effects on tumor oxygenation and combination treatments require clarification.

Purpose of the Study:

  • To investigate the early effects of vandetanib, a VEGFR inhibitor, on tumor oxygenation and its impact on combining vandetanib with radiotherapy.
  • To assess how vandetanib influences tumor oxygen consumption, perfusion, and radiation sensitivity.

Main Methods:

  • Utilized transplantable liver tumors in mice, administering daily doses of vandetanib (25 mg/kg).
  • Measured tumor oxygenation (pO(2)) and cellular oxygen consumption via electron paramagnetic resonance (EPR).
  • Assessed tumor perfusion using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and evaluated radiation sensitivity through regrowth delay assays.

Main Results:

  • Vandetanib treatment led to an early increase in tumor oxygenation, independent of vascular remodeling or perfusion changes.
  • A significant decrease in tumor cell oxygen consumption was observed, likely causing the increased oxygenation.
  • Vandetanib potentiated the tumor response to radiotherapy, consistent with improved oxygenation.

Conclusions:

  • Inhibitors of VEGFR signaling, such as vandetanib, reduce tumor cell oxygen consumption rates.
  • The observed early increase in tumor oxygenation by vandetanib has significant implications for optimizing the timing and sequencing of combination therapies involving VEGF inhibitors and radiation.

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