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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR002584-24
Application #
8363897
Study Section
Special Emphasis Panel (ZRG1-SBIB-U (40))
Project Start
2011-09-01
Project End
2012-07-31
Budget Start
2011-09-01
Budget End
2012-07-31
Support Year
24
Fiscal Year
2011
Total Cost
$8,049
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Funk, Alexander M; Anderson, Brian L; Wen, Xiaodong et al. (2017) The rate of lactate production from glucose in hearts is not altered by per-deuteration of glucose. J Magn Reson 284:86-93
Mishkovsky, Mor; Anderson, Brian; Karlsson, Magnus et al. (2017) Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized 13C magnetic resonance. Sci Rep 7:11719
Moreno, Karlos X; Harrison, Crystal E; Merritt, Matthew E et al. (2017) Hyperpolarized ?-[1-13 C]gluconolactone as a probe of the pentose phosphate pathway. NMR Biomed 30:
Zhang, Liang; Habib, Amyn A; Zhao, Dawen (2016) Phosphatidylserine-targeted liposome for enhanced glioma-selective imaging. Oncotarget 7:38693-38706
Malloy, Craig R; Sherry, A Dean (2016) Biochemical Specificity in Human Cardiac Imaging by 13C Magnetic Resonance Imaging. Circ Res 119:1146-1148
Wu, Yunkou; Zhang, Shanrong; Soesbe, Todd C et al. (2016) pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent. Magn Reson Med 75:2432-41
Walker, Christopher M; Merritt, Matthew; Wang, Jian-Xiong et al. (2016) Use of a Multi-compartment Dynamic Single Enzyme Phantom for Studies of Hyperpolarized Magnetic Resonance Agents. J Vis Exp :e53607
Moss, Lacy R; Mulik, Rohit S; Van Treuren, Tim et al. (2016) Investigation into the distinct subcellular effects of docosahexaenoic acid loaded low-density lipoprotein nanoparticles in normal and malignant murine liver cells. Biochim Biophys Acta 1860:2363-2376
Xing, Yixun; Jindal, Ashish K; Regueiro-Figueroa, Martín et al. (2016) The Relationship between NMR Chemical Shifts of Thermally Polarized and Hyperpolarized 89 Y Complexes and Their Solution Structures. Chemistry 22:16657-16667
Jin, Eunsook S; Moreno, Karlos X; Wang, Jian-Xiong et al. (2016) Metabolism of hyperpolarized [1-(13)C]pyruvate through alternate pathways in rat liver. NMR Biomed 29:466-74

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