The feasibility of assessing branched-chain amino acid metabolism in cellular models of prostate cancer with hyperpolarized [1-C]-ketoisocaproate |
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| Authors: | Kelvin L Billingsley Jae Mo Park Sonal Josan Ralph Hurd Dirk Mayer Eleanor Spielman-Sun Dwight G Nishimura James D Brooks Daniel Spielman |
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| Institution: | 1. Department of Chemistry & Biochemistry, San Francisco State University, San Francisco, CA 94132, USA;2. Department of Radiology, Stanford University, Stanford, CA 94305, USA;3. Neuroscience Program, SRI International, Menlo Park, CA 94025, USA;4. Applied Sciences Laboratory, GE Healthcare, Menlo Park, CA 94025, USA;5. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland–Baltimore, Baltimore, MD 21201, USA;6. Department of Chemistry, Oberlin College, Oberlin, OH 44074, USA;g Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA;h Department of Urology, Stanford University, Stanford, CA 94305, USA |
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| Abstract: | Recent advancements in the field of hyperpolarized 13C magnetic resonance spectroscopy (MRS) have yielded powerful techniques capable of real-time analysis of metabolic pathways. These non-invasive methods have increasingly shown application in impacting disease diagnosis and have further been employed in mechanistic studies of disease onset and progression. Our goals were to investigate branched-chain aminotransferase (BCAT) activity in prostate cancer with a novel molecular probe, hyperpolarized 1-13C]-2-ketoisocaproate (1-13C]-KIC), and explore the potential of branched-chain amino acid (BCAA) metabolism to serve as a biomarker. Using traditional spectrophotometric assays, BCAT enzymatic activities were determined in vitro for various sources of prostate cancer (human, transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse and human cell lines). These preliminary studies indicated that low levels of BCAT activity were present in all models of prostate cancer but enzymatic levels are altered significantly in prostate cancer relative to healthy tissue. The MR spectroscopic studies were conducted with two cellular models (PC-3 and DU-145) that exhibited levels of BCAA metabolism comparable to the human disease state. Hyperpolarized 1-13C]-KIC was administered to prostate cancer cell lines, and the conversion of 1-13C]-KIC to the metabolic product, 1-13C]-leucine (1-13C]-Leu), could be monitored via hyperpolarized 13C MRS. |
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| Keywords: | Hyperpolarized carbon-13 Dynamic nuclear polarization Magnetic resonance spectroscopy/spectroscopic imaging Prostate cancer Branched-chain aminotransferase |
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