Imaging tumor hypoxia by magnetic resonance methods

Abstract

Tumor hypoxia results from the negative balance between the oxygen demands of the tissue and the capacity of the neovasculature to deliver sufficient oxygen. The resulting oxygen deficit has important consequences with regard to the aggressiveness and malignancy of tumors, as well as their resistance to therapy, endowing the imaging of hypoxia with vital repercussions in tumor prognosis and therapy design. The molecular and cellular events underlying hypoxia are mediated mainly through hypoxia-inducible factor, a transcription factor with pleiotropic effects over a variety of cellular processes, including oncologic transformation, invasion and metastasis. However, few methodologies have been able to monitor noninvasively the oxygen tensions in vivo. MRI and MRS are often used for this purpose. Most MRI approaches are based on the effects of the local oxygen tension on: (i) the relaxation times of 19F or 1H indicators, such as perfluorocarbons or their 1H analogs; (ii) the hemodynamics and magnetic susceptibility effects of oxy- and deoxyhemoglobin; and (iii) the effects of paramagnetic oxygen on the relaxation times of tissue water. 19F MRS approaches monitor tumor hypoxia through the selective accumulation of reduced nitroimidazole derivatives in hypoxic zones, whereas electron spin resonance methods determine the oxygen level through its influence on the linewidths of appropriate paramagnetic probes in vivo. Finally, Overhauser-enhanced MRI combines the sensitivity of EPR methodology with the resolution of MRI, providing a window into the future use of hyperpolarized oxygen probes. Tumor hypoxia has important consequences in the aggressiveness and malignancy of tumors, as well as in their resistance to therapy, endowing the imaging of pO2 levels with vital repercussions in tumor prognosis and therapy design. This review introduces the causes and consequences of tumor hypoxia and describes the main MR techniques implemented to visualize oxygen levels in cancers. The figure illustrates the MRI oximetry of H460 human tumor xenografts from rats breathing air or oxygen as obtained using perfluorocarbon methodology. Copyright © 2010 John Wiley & Sons, Ltd.