We investigated the early effects of vandetanib (ZACTIMA™; ZD6474), an inhibitor of VEGFR-dependent angiogenesis, on tumor oxygenation and on the possible consequences of combining vandetanib with radiotherapy. Tumor oxygenation, perfusion, cellular consumption of oxygen, and radiation sensitivity were studied in transplantable liver tumors after daily doses of vandetanib (25 mg kg−1 i.p.). Measurements of oxygenation (pO2) and tumor cell oxygen consumption were carried out using electron paramagnetic resonance (EPR), and perfusion parameters were assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Regrowth delay assays were performed after treatment with vandetanib alone, radiation alone or a combination of both treatments. Vandetanib induced an early increase in tumor oxygenation that did not correlate with remodeling of the tumor vasculature or with changes in tumor perfusion. A decrease in tumor cell oxygen consumption was observed that could have been responsible for this increase in tumor oxygenation. Consistent with this increase in tumor oxygenation, we found that vandetanib potentiated the tumor response to radiotherapy. Our results confirm that treatment with an inhibitor of VEGFR signaling reduces oxygen consumption rate by tumor cells. The observation that vandetanib causes an early increase in tumor oxygenation has implications for the timing and sequencing of treatment with VEGF signaling inhibitors in combination with radiation.
You have requested a machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Neither BioOne nor the owners and publishers of the content make, and they explicitly disclaim, any express or implied representations or warranties of any kind, including, without limitation, representations and warranties as to the functionality of the translation feature or the accuracy or completeness of the translations.
Translations are not retained in our system. Your use of this feature and the translations is subject to all use restrictions contained in the Terms and Conditions of Use of the BioOne website.