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

• Published in: Molecular imaging and biology Vol. 13; no. 6; pp. 1107 - 1113
• Main Authors: Elas, Martyna, Hleihel, Danielle, Barth, Eugene D., Haney, Chad R., Ahn, Kang-Hyun, Pelizzari, Charles A., Epel, Boris, Weichselbaum, Ralph R., Halpern, Howard J.
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.12.2011; Springer Nature B.V
• Subjects: Animals; Cell Hypoxia; Diagnostic Imaging - methods; Electron Spin Resonance Spectroscopy - methods; Humans; Imaging; Medicine; Medicine & Public Health; Mice; Neoplasms - metabolism; Neoplasms - pathology; Oxygen - metabolism; Partial Pressure; Radiology; Research Article; Vascular Endothelial Growth Factor A - metabolism; EPR oxygen images; EPR; VEGF; Oxygen heterogeneity; Hypoxia; Image-guided therapy; Tumor oxygenation
• ISSN: 1536-1632; 1860-2002; 1860-2002
• DOI: 10.1007/s11307-010-0436-4

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.