摘要

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.

  • 出版日期2014-8