Bench-To-Bedside Oximetry for Real-Time Monitoring of Tumor Po2 : A Critical Parameter Which Influences Radiotherapeutic Outcome - Abstract
Tumor hypoxia (pO2; partial pressure of oxygen < 10 – 15 mmHg) plays a critical role in radio-resistance and promotes the development of aggressive tumor phenotypes. Furthermore, tumor hypoxia is dynamic and varies with tumor type, stage and as a consequence of ionizing radiation and other therapies.
In spite of its profound effect on treatment outcome, tumor pO2has been sub-optimally exploited in radiation oncology. Current radiotherapy plans do not take into account specific temporal changes in individual tumor pO2levels due to lack of appropriate oximetry techniques, and therefore potentially may be suboptimal. In particular, hypofractionated treatments are increasingly used with large doses (4 - 20 Gy) of ionizing radiation that may have different effects on the levels of oxygen in individual tumors during the course of treatment. Real-time monitoring of tumor pO2might make it feasible to improve the outcome by scheduling fractions at times of increased tumor pO2. Such tumor oxygen guided treatment protocols can only be accomplished by oximetry techniques that can provide accurate serial measurements of tumor pO2throughout the course of therapy.
We have pioneered in vivo EPR oximetry using micro-particulate oxygen-sensing probes for real-time monitoring of tissue pO2in superficial (<10 mm) as well as deep-sited tumors, repeatedly and accurately, for clinical applications. Our goal is to improve treatment outcome by providing the information about dynamic tumor oxygen levels so that irradiations can be scheduled when the tumors are better oxygenated either with or without oxygen enhancing interventions e. g. pre-irradiation, carbogen (2 - 5% CO2 balance O2 ) inhalation, hyperthermia, and anti-angiogenic treatment. Temporal changes in tumor
pO2 can also be used as a prognostic marker to predict efficacy, identify responders and non-responders, and individualize therapy. An overview of in vivo EPR oximetry, pre-clinical results and the current status of clinical oximetry are briefly described to highlight the potential advantages of EPR oximetry in radiation oncology.