Abstract
1128
Introduction: Tissues with low levels of oxygen often respond poorly to radiation therapy and chemo / immune therapies. Hypoxia in tumor bearing tissue is associated with worse clinical outcome and this has been known for over 50 years. Alterations to radiation therapy planning via providing localized boost to hypoxic tissues cannot be made without knowing exactly where hypoxia exists. However, there is no FDA approved agent to assess for hypoxia in tumor tissues, there is no accepted standard methodology for measuring hypoxia in patients, nor are there FDA approved agents for treating hypoxia. There are multiple PET imaging agents that can find areas of hypoxia in tumors .These include 18F MISO (which becomes irreversibly bound to hypoxic cells and trapped over time) and 18F FAZA (newer and has more ideal imaging qualities, though uptake could in part be flow related). Both of these agents require cells to be viable as part of uptake. There are several copper containing PET imaging compounds such as 62Cu-ATSM which become trapped due to the redox environment of hypoxic tissues. Cu-ATSM uptake can be associated with over expression of VEGF. However, radiation dose from the copper containing compounds is about 2X that of 18F MISO. Distribution of Cu-ATSM is not the same as FMISO, and the role for Cu-ATSM compounds vs FMISO is not clear. There also are also several MRI techniques such as OE, DCE, BOLD, qBOLD, and TOLD that can be used to assess for hypoxia. None have achieved any broad clinical use. PET tracers often suffer from poor target to background ratios. MRI advantages include lower cost and greater availability, as there is no specialty imaging agent to produce. Some techniques such as DCE are already widely available, even at remote community centers. The ideal means of assessing hypoxia would be non-invasive, reproducible, have good spatial and temporal resolution, along with low cost. If the current challenges to hypoxia imaging could be surmounted, it would likely have a wide beneficial effect of improving outcome of therapy, although clinical trials would be first be required to confirm this. The significance of the problem is enormous, as at least half of all locally invasive solid tumors likely harbor zones of anoxia or hypoxia. Localization of hypoxia would also be very important outside of oncology, for example in assessment of cerebro-vascular stroke (CVA) and myocardial damage due to MI.