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

PurposeTumor microenvironments show remarkable tumor pO2 heterogeneity, as seen in prior EPR pO2 images (EPROI). pO2 correlation with hypoxia response proteins is frustrated by large rapid pO2 changes with position.ProceduresTo 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 pO2.ResultsQuantitative ELISA VEGF concentrations correlated (p = 0.0068 to 0.019) with mean pO2, median pO2, and the fraction of voxels in the biopsy volume with pO2 less than 3, 6, and 10 Torr.ConclusionsThis 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.

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