13C Magnetic Resonance Imaging and Hyperpolarization Techniques for High-Resolution In vivo pH Mapping in Preclinical Models of Prostate Cancer
- Author(s): Korenchan, David Edward
- Advisor(s): Kurhanewicz, John
- et al.
Interstitial acidification in the context of prostate cancer may serve as a biomarker of low-to-high grade transition, in addition to providing useful information for predicting therapeutic response. Therefore, a noninvasive imaging technique to accurately map interstitial pH may serve as a powerful tool for informing clinical decision-making regarding cancer. Although hyperpolarized 13C spectroscopic imaging using [13C]bicarbonate as an imaging agent can produce interstitial pH maps in vivo, initially reported methods yielded insufficient signal-to-noise for high-resolution pH mapping. Technical innovation has thus been required in order to boost available imaging signal and improve spatial resolution.
This dissertation encapsulates the development of new imaging agents, hyperpolarization strategies, and pulse sequence approaches in pursuit of clinically translatable interstitial pH imaging approaches. A strategy to generate hyperpolarized [13C]bicarbonate via rapid hydrolysis of a high-polarization, high-concentration precursor molecule, [1-13C]1,2-glycerol carbonate, was developed. This precursor approach, coupled with pulse sequences that mitigate signal loss and pH inaccuracies due to bicarbonate-CO2 chemical exchange, demonstrated good SNR in smaller voxels for hyperpolarized 13C imaging at 14 T. As an alternative approach to hyperpolarized pH imaging, two new pH imaging agents, potentially more amenable to high-resolution imaging than [13C]bicarbonate, were discovered and subsequently developed for highly accurate pH imaging in phantoms. These technical developments include low-toxicity molecular approaches and demonstrate potential for generating appropriate agent concentrations and polarizations for use in humans. They are therefore expected to enable eventual clinical translation of hyperpolarized pH imaging and lay the foundation for further study of pH, perfusion, and metabolism in the context of prostate cancer.