This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The goal of this research is to gain a comprehensive understanding of tumor physiology as related to tumor growth, development and response to therapy. A number of nonNMR approaches such as optical techniques are under development, However, we continue to pursue our MRI efforts related to measurement of oxygen tension and enzyme activation. We use fluorinated substrates of specific enzymes and take advantage of the fact that the 19F chemical shift will shift with hydrolysis, and the absence of a 19F background allows simple detection by NMR of the reaction. Our other object is to focus on oxygen tension and the dynamic response to interventions, perfusion and transmembrane pH. Oxygen dynamics are detected using FREDOM, a 19F MRI method using hexafluorobenzene as a reporter molecule, which we have developed over the past several years. This allows us to generate quantitative maps of tumor oxygen tension and to assess local response to interventions. Most significantly, we have now shown that measured changes in oxygen tension accompanying interventions correctly predict enhanced therapeutic outcome (radiation induced growth delay). Tumor perfusion is assessed by dynamic contrast enhancement and BOLD (Blood Oxygen Level Dependant contrast) 1H MRI. This is a large group with interactions across the campus including Dr. Vikram Kodibagkar, Dr. Luis Parada, and Dr. Hanli Liu.
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