Guiding radiation therapy based on local tissue oxygen measurements is critically important as hypoxia (low oxygen) in the tumor microenvironment has been shown to be a strong indicator of increased cancer progression and tumor radiation resistance, so the ability to guide radiation therapy based on local tissue oxygen measurements would potentially improve radiation therapy efficacy. The primary mechanism of radiation is the creation of free radicals that damage the tumor cell DNA. These radicals are neutralized by sulfhydryl containing compounds present in hypoxic cells allowing repair of DNA and leading to treatment failure. Hypoxia radiation resistance is prevalent in most solid tumors, particularly in head and neck, prostate, and cervix. For instance, 48% of all cervical cancers are characterized as hypoxic and those have a reduced 6-year overall survival of 29% compared to 87% for non-hypoxic cases. Overcoming therapy resistance in these cases requires personalized treatment strategies to deliver higher radiation doses to regions with low oxygen levels, increase tumor oxygen levels and optimal time of radiation to enhance effectiveness of radiation therapy. Although the benefits of hypoxia-based treatment prescriptions have been demonstrated in preclinical models, translating these findings into humans has been challenged by the lack of a method to reliably and repeatedly measure oxygen levels within these tumors. Existing oxygen measurement techniques are inadequate for personalizing treatment because they either involve impractical invasiveness or workflow changes, cannot be repeated in a clinically meaningful timeframe, require expensive imaging equipment and trained personnel or provide only indirect and qualitative information.

Our objective is to develop first clinically viable technology for Oxygen-Guided Radiation Therapy (OGRT) to personalize radiation treatment. To achieve this, we will exploit the unique capabilities of electron paramagnetic resonance (EPR) to provide fast, direct, and repeated tissue oxygen measurements to inform clinical decision-making. Electron paramagnetic resonance (EPR) oximetry is an ideal method for measuring hypoxia with its unique capability of rapidly providing precise and absolute tissue oxygenation values without radioactive agents or costly medical imaging systems. EPR uses an oxygen sensing material and an EPR radiofrequency (RF) microcoil to measure local partial pressure of oxygen. EPR can be acquired at a rapid rate, enabling repeated measurements to provide oximetry measurements immediately before and during interventions. The need for invasive implantation has limited its use to relatively superficial tumors (<1cm). We have recently made advances in EPR microcoil technology (patent pending) capable of measuring the local oxygenation levels in deep tumors (~30 cm). This technology will enable personalization of radiation treatments by intensifying treatment in hypoxic regions, thereby enhancing treatment outcomes with reduced toxicity, interventions to enhance tumor oxygen and delivery of radiation at the time of peak tumor oxygen which requires fast and repeated oxygen measurements; that is one of the key strengths of our technology.