Tumor hypoxia is recognized as a limiting factor for the efficacy of radiotherapy, because it enhances tumor radioresistance. It is strongly suggested that assessing tumor oxygenation could help to predict the outcome of cancer patients undergoing radiation therapy. Strategies have also been developed to alleviate tumor hypoxia in order to radiosensitize tumors. In addition, oxygen mapping is critically needed for intensity modulated radiation therapy (IMRT), in which the most hypoxic regions require higher radiation doses and the most oxygenated regions require lower radiation doses. However, the assessment of tumor oxygenation is not yet included in day-to-day clinical practice. This is due to the lack of a method for the quantitative and non-invasive mapping of tumor oxygenation. To fully integrate tumor hypoxia parameters into effective improvements of the individually tailored radiation therapy protocols in cancer patients, methods allowing non-invasively repeated, safe, and robust mapping of changes in tissue oxygenation are required. In this review, non-invasive methods dedicated to assessing tumor oxygenation with the ultimate goal of predicting outcome in radiation oncology are presented, including positron emission tomography used with nitroimidazole tracers, magnetic resonance methods using endogenous contrasts (R1 and R2*-based methods), and electron paramagnetic resonance oximetry; the goal is to highlight results of studies establishing correlations between tumor hypoxic status and patients’ outcome in the preclinical and clinical settings.

MOBILE arises as a promising noninvasive and sensitive tool for diagnosis and therapeutic guidance in disorders involving hypoxia.

Purpose: Although hypoxia has been long recognized as a crucial factor impairing tumor response in many therapeutic schemes, atraumatic and reliable methods of individually quantifying tumor oxygenation are still lacking in day-to-day clinical practice. The aim of this work was to investigate the potentially quantitative properties of our recently described noninvasive magnetic resonance (MR) technique "MOBILE" (mapping of oxygen by imaging lipids relaxation enhancement) and to qualify this endogenous contrast as a tumor hypoxia marker.Experimental Design: The "MOBILE" technique, which assesses the longitudinal MR relaxation rate, R 1 , of lipid protons, was benchmarked with the parent technique which assesses the global (or water) R 1 , in response to a hyperoxic challenge (carbogen breathing) and to a hypoxic challenge (combretastatin A4) in MDA-MB-231 xenografts and in NT2 mammary tumors. Electron paramagnetic resonance (EPR) oximetry was used to quantitatively assess the tumor pO 2 in matching tumors longitudinally.Results and Conclusion: Our study evidenced that (i) positive and negative changes in tumor oxygenation can be detected using MOBILE; (ii) a change in the R 1 of lipids is positively correlated with a change in the tumor pO 2 (P ¼ 0.0217, r ¼ 0.5097); (iii) measured lipid R 1 values are positively correlated with absolute pO 2 values in both tumor models (P ¼ 0.0275, r ¼ 0.3726); and (iv) changes in the R 1 of lipids are more sensitive than changes in the global R 1 . As this technique presents unique translational properties, it seems promising for the individual longitudinal monitoring of tumor oxygenation in a clinical setting.

MOBILE was identified as a marker to follow a decrease in oxygenation induced by CA4. However, DCE-MRI showed a higher dynamic range to follow changes in tumor hemodynamics induced by CA4.

Phase imaging seems to be an appropriate means to measure the AIF of mice at high field.