In the current study, radiation of glioma xenografts led to induction of hypoxia-inducible factor (HIF)-1 as measured in vivo by HIF-1 dependent PET imaging. PX-478 inhibited this induction of HIF-1 following radiation and sensitized tumor blood vessels to durable radiation-mediated disruption.
Quantitative analyses of glioma cells treated with PX-478 and radiation showed a significant decrease in levels of HIF-1 alpha protein and vascular endothelial growth factor compared with radiation alone. PX-478 in combination with radiation inhibited tumor growth more potently than either modality alone. PX-478 was also shown to enhance the inhibition of tumor growth by radiation in two pancreatic cancer models.