This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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. Specifically, we will develop, demonstrate, and evaluate a novel approach to assessing tumor oxygenation with a view to rapid translation to the clinic. We believe it will be most pertinent to high dose hypofractionated radiotherapy in diseases such as prostate cancer. DOCENT (Dynamic Oxygen Challenge Evaluated by NMR T1 and T2*) exploits BOLD (blood oxygen level dependent) and TOLD (tissue oxygen level dependent) contrast to non-invasively detect changes in tumor oxygenation using proton MRI. We propose to develop DOCENT as a robust prognostic test to reveal tumor hypoxia. While the investigations proposed here are entirely pre-clinical, we believe they will demonstrate a strong rationale for rapid implementation in patients.
Aim 1 will rigorously demonstrate the ability of DOCENT to categorize tumors as hypoxic (resistant or responsive) or oxic by comparison with 19F MR oximetry.
Aim 2 will examine whether DOCENT does indeed predict response to hypofractionated radiation in subcutaneously growing prostate tumors.
Aim 3 will extend studies to orthotopic prostate tumors.
Aim 4 will seek to overcome therapeutic resistance of hypoxic tumors by including a radiation boost.
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