Where It’s at Really Matters: In Situ In Vivo Vascular Endothelial Growth Factor Spatially Correlates with Electron Paramagnetic Resonance pO(2) Images in Tumors of Living Mice

PURPOSE: Tumor microenvironments show remarkable tumor pO(2) heterogeneity, as seen in prior EPR pO(2) images (EPROI). pO(2) correlation with hypoxia response proteins is frustrated by large rapid pO(2) changes with position. PROCEDURES: To overcome this limitation, biopsies stereotactically located in the EPROI were used to explore the relationship between vascular endothelial growth factor A (VEGF) concentrations in living mouse tumors and the local EPROI pO(2). RESULTS: Quantitative ELISA VEGF concentrations correlated (p = 0.0068 to 0.019) with mean pO(2), median pO(2), and the fraction of voxels in the biopsy volume with pO(2) less than 3, 6, and 10 Torr. CONCLUSIONS: This validates EPROI hypoxic fractions at the molecular level and provides a new paradigm for the assessment of the relationship, in vivo, between hypoxia and hypoxia response proteins. When translated to human subjects, this will enhance understanding of human tumor pathophysiology and cancer response to therapy.