Absolute oxygen R 1e imaging in vivo with pulse electron paramagnetic resonance

Purpose Tissue oxygen (O 2 ) levels are among the most important and most quantifiable stimuli to which cells and tissues respond through inducible signaling pathways. Tumor O 2 levels are major determinants of the response to cancer therapy. Developing more accurate measurements and images of tissue O 2 partial pressure (pO 2 ), assumes enormous practical, biological, and medical importance. Methods We present a fundamentally new technique to image pO 2 in tumors and tissues with pulse electron paramagnetic resonance (EPR) imaging enabled by an injected, nontoxic, triaryl methyl (trityl) spin probe whose unpaired electron's slow relaxation rates report the tissue pO 2 . Heretofore, virtually all in vivo EPR O 2 imaging measures pO 2 with the transverse electron spin relaxation rate, R 2e , which is susceptible to the self‐relaxation confounding O 2 sensitivity. Results We found that the trityl electron longitudinal relaxation rate, R 1e , is an order of magnitude less sensitive to confounding self‐relaxation. R 1e imaging has greater accuracy and brings EPR O 2 images to an absolute pO 2 image, within uncertainties. Conclusion R 1e imaging more accurately determines oxygenation of cancer and normal tissue in animal models than has been available. It will enable enhanced, rapid, noninvasive O 2 images for understanding oxygen biology and the relationship of oxygenation patterns to therapy outcome in living animal systems. Magn Reson Med 72:362–368, 2014. © 2013 Wiley Periodicals, Inc.