Prostate cancers demonstrate a tremendous range in biologic diversity and the current clinical assessment of response to non-surgical therapy is often inadequate because studies have shown inaccuracies when relying upon serum prostate specific antigen (PSA) levels reaching a nadir or upon the histological confirmation of cancer using transrectal ultrasound guided biopsies. There remains a critical clinical need for more sensitive and specific molecular imaging biomarkers of prostate cancer presence, aggressiveness, hormonal status and early response to therapy. 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. The objective of this early stage clinical trial in imaging is to characterize the reproducibility of this new technique,HP MR with [1-13C] pyruvate in 2 cohorts of prostate cancer patients. In the first cohort (n = 20), patients will be imaged twice in less than 3 weeks using a dynamic magnetic resonance spectroscopy sequence (Dynamic). This data will be used to determine the variability in biomarker dynamics and their delivery to the gland. In a second cohort (n = 20), patients will be imaged twice, analogous to the first cohort, using a high-resolution three- dimensional MR spectroscopic imaging sequence (3D MRSI) in order to determine the reproducibility of HP biomarkers across the entire prostate and assess the relationship between HP Lactate and prostate cancer biology. It is the overarching goal of this proposal to determine the reproducibility of HP pyruvate metabolic imaging in patients, which can be used as a benchmark for future studies using this technique, and 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 by applying it with the agent HP [1-13C] pyruvate in patients with prostate cancer. 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 validate the reproducibility of HP pyruvate in a cohort of prostate cancer patients and this work will aid in future patient-specific treatment planning, facilitate earlier assessment of response to therapy, and aid the development of novel experimental strategies for cancer treatment.
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| Miloushev, Vesselin Z; Granlund, Kristin L; Boltyanskiy, Rostislav et al. (2018) Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. Cancer Res 78:3755-3760 |
| Miloushev, Vesselin Z; Di Gialleonardo, Valentina; Salamanca-Cardona, Lucia et al. (2017) Hyperpolarized 13C pyruvate mouse brain metabolism with absorptive-mode EPSI at 1T. J Magn Reson 275:120-126 |
| Lin, Gigin; Keshari, Kayvan R; Park, Jae Mo (2017) Cancer Metabolism and Tumor Heterogeneity: Imaging Perspectives Using MR Imaging and Spectroscopy. Contrast Media Mol Imaging 2017:6053879 |
