Is R1 of Lipids related to pO2? Lessons from two tumor models

Introduction: Tumor hypoxia is acknowledged as a major factor of resistance of solid tumors to treatment. Improving tumor oxygenation at the time of treatment could lead to an improved response to both chemotherapy and radiotherapy. Variations in T1 and T2* are potentially valuable MRI tools to follow changes in tumor oxygenation. T2* is sensitive to the relative Hb/HbO2 ratio in vessel , while T1 change is sensitive to dissolved oxygen which acts as a T1shortening paramagnetic contrast agent. The aim of the current work is to investigate the quantitative aspect of a new oxygen mapping method: MOBILE (Mapping of Oxygen By Lipids relaxation Enhancement). This non-invasive method is based on the changes in the relaxation properties of the tissue lipids by exploiting the higher solubility property of oxygen in lipids than in water. For this purpose, two tumor models were submitted to (i) hyperoxic challenges induced by carbogen breathing and (ii) hypoxic challenges induced by Combetastatin A-4 Phosphate, a vascular disrupting agent (VDA) known to induce hypoxia within 3 hours. Actual pO2 was obtained by EPR oximetry. We compared sensitivities of the MOBILE technique with the classical ‘oxygen enhanced MRI’ sensitivity that measures global T1 mainly influenced by water protons.