Where It’s at Really Matters: In Situ In Vivo Vascular Endothelial Growth Factor Spatially Correlates with Electron Paramagnetic Resonance pO2 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.