Targeting the Acidic Microenvironment of Prostate Cancer Using Chemical Shift Based, Clinically Translatable Hyperpolarized 13C MRI Biomarkers
Technical Report,01 Aug 2017,31 Jul 2018
University of California San Francisco United States
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Prostate cancer has a heterogeneous disease course. Distinguishing between the different phenotypes of prostate cancer is an important problem for clinical oncologists. Non-invasive biomarkers that would not only characterize prostate cancer aggressiveness but also predict response to therapy would be of enormous benefit to patients. One potential prognostic imaging biomarker is acidic interstitial pH, which has been shown to be associated with local invasion and metastases in a variety of cancers. The central hypothesis of this proposal is that low interstitial pH is strongly correlated with both tumoral lactate generation and tumor aggressiveness. We propose to investigate, using hyperpolarized HP 13C magnetic resonance spectroscopy MRS, the relationship of lactate export to extracellular matrix acidification, establish pH as a critical determinant of cancer aggressiveness and use new HP platforms to target tumor acidity with the long-term aim to develop new clinically-translatable HP imaging approaches. The Specific aim 1 is to develop new classes of HP 13C agents for probing interstitial pH. The Specific Aim 2 is to validate the efficiency of the new HP 13C agents for MRI. The Specific aim 3 is to investigate the relationship between HP lactate generation and acidic interstitial pH. We will correlate HP pH maps to lactate generation and efflux and show grade-dependent changes in tumoral acidity.
- Medicine and Medical Research