Tumor oxygenating treatments (TOX's) have the potential to substantially improve tumor response to therapy. However, despite some successes, the ability of TOX's to help a large percentage of cancer patients has been disappointing. The reasons for this are difficult to determine because there is currently no method routinely used to directly image changes in tumor oxygen tension caused by TOX's. Development of improved TOX's and their clinical application would be greatly facilitated by such measurements. We previously demonstrated a strong correlation in rodent tumors between decreases in the linewidth (i.e. increases in T2 ) of the MR water signal caused by TOX's and increases in tumor pO2 measured by microelectrode- averaged over the entire tumor. However, the spatial resolution of MR measurements has not been evaluated. Spatial resolution is important because the effectiveness of TOX's may be limited by the non-uniformity of their effects. Therefore, we propose to optimize and evaluate the spatial resolution of MR measurements of effects of TOX's by correlating MR data with spatially resolved measurements of pO2 made with established, quantitative methods: A. Perfluorocarbon emulsions (PFCs) will be injected I.V. or intratumorally and taken up into tumors over a period of days. The T1 of the fluorine nucleus in the PFC micelle is a sensitive index of local pO2. Therefore 19F MRI will be provide high resolution images of tumor pO2 before, during, and after treatment with TOX's. These data will be correlated with changes in T2 measured by 1H MRI. B. Oxygen microelectrodes will be used as an additional quantitative check on the fluorine MR measurements. Microelectrode measurements of pO2 before, during, and after TOX treatments will be compared to 19F and 1H MRI data averaged over the same regions. The proposed experiments are likely to lead rapidly to clinical applications of this new technology.

R01CA075476

1999-09-01

2003-06-30