Tumor Hypoxia

As we enter the age of personalized medicine, it becomes increasingly important to characterize tumors for potential response to therapy. Hypoxia is recognized to influence solid tumor response to therapy and has been related to tumor aggressiveness, including growth, development, and metastatic potential.

Hypoxia is a hallmark of tumor pathophysiology, but its routine non-invasive assessment in vivo remains elusive. Immunohistochemical and invasive electrode studies have revealed tumor hypoxia and its influence on therapeutic response. Non-invasive measurement would be far more attractive and oxygen-enhanced MRI promises insights into tumor hypoxia both for pre-clinical evaluation and ready translation to patients. The ability to stratify patients according to the oxygen characteristics of a tumor becomes increasingly relevant with the development of high dose stereotactic ablation radiation therapy (SABR). We believe we are at a historic juncture, where we not only have technologies for identifying hypoxia, but more importantly methods of tailoring therapy successfully to accommodate or exploit the killing of hypoxic cells.

As a corollary to identifying hypoxia to stratify patients for optimal therapy, there is a pressing need to effectively apply adjuvant interventions to modify response. Historical misanalyses indicate marginal benefit for interventions designed to modify hypoxia, with the general conclusion that success was limited by inability to identify those patients who would benefit.

We have been developing methods to assess tumor oxygenation, which now provide robust validated techniques for pre-clinical assessment of tumor heterogeneity and dynamic response to interventions based on ¹⁹F MRI of the reporter molecule hexafluorobenzene. We have recently focused on practical oximetry methods for translation to the clinical arena and focus on oxygen enhanced proton MRI interrogating tissue water itself. Indeed, we have also initiated translation to patients and demonstrate feasibility and relevance in preliminary human applications.