Prostate cancers, currently the most common cancer in men, demonstrate a tremendous range of biologic diversity. Clinical assessments of response to non-surgical therapy are often inadequate because, as studies have shown, they lead to inaccuracies when they rely upon serum prostate specific antigen (PSA) levels reaching a nadir, or upon the histological confirmation of cancer using transrectal ultrasound guided biopsies. When progressing to metastatic cancer, typically after androgen deprivation therapy, castrate resistant prostate cancer (CRPC) results in bone lesions in more than 90% of cases. There remains a critical clinical need for greater sensitivity and specificity in molecular imaging biomarkers of prostate cancer presence and of response to novel therapeutics. An extraordinary new technique, hyperpolarized magnetic resonance (HP MR), has the potential to change the way we interrogate metabolism in vivo. Through the utilization of 13C-labeled endogenous substrates, we are able to non-invasively image a metabolic intermediate and its subsequent downstream products using conventional MRI. In the setting of prostate cancer, this provides a potentially invaluable tool for the study of prostate cancer metabolism and its modulation as a function of tumor aggressiveness and response to therapeutic intervention. Unfortunately, we are currently limited in our ability to visualize large volumes of interest, whereas metastatic prostate cancer typically requires visualization of the abdomen and bone regions, virtually inaccessible to current HP MRI approaches. The objective of this innovative academic industrial partnership is to address this problem by developing a large-field-of-view HP MRI approach, including both hardware and software. This proposal would establish a robust platform to enable the imaging of metastatic disease in prostate cancer patients. In the first aim of this proposal we will develop a novel 13C body transmit coil and receive system capable of imaging the abdomen. In tandem, we will also develop acquisition strategies to take advantage of this hardware for rapid HP MRI. Finally, we will validate this approach in 2 cohorts of metastatic prostate cancer patients. The first will be imaged with HP [1-13C] pyruvate to assess methods to visualize downstream glycolysis and the second with [2-13C] pyruvate to image the TCA cycle for a first-in-human study. It is the overarching goal of this proposal to build a novel, large-field-of-view approach to HP MRI ? including, importantly, both hardware and software ? and apply it to the imaging of HP pyruvate metabolism in cancer patients so as to provide benchmark for future studies using this technique, and additionally to determine its ability to inform on prostate biology.
The over-arching goal of the proposed research is to translate a new MRI technology, hyperpolarized (HP) MR, to the clinic in the setting of large-field-of-view (FOV) MRI, which utilizes both the agents HP [1-13C] pyruvate and [2-13C] pyruvate in metastatic prostate cancer patients. Prostate cancer demonstrates tremendous biologic diversity, and there is an urgent need to develop more sensitive and specific imaging biomarkers to characterize the disease. We aim to develop a large-body transmit/receive system and pulse sequences for large FOV and apply them to a cohort of prostate cancer patients: this work will aid in future patient-specific treatment planning, facilitate earlier assessment of response to therapy, and facilitate the development of novel experimental strategies for cancer treatment.
