期刊
MAGNETIC RESONANCE IMAGING
卷 32, 期 7, 页码 791-795出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.mri.2014.04.015
关键词
Hyperpolarized carbon-13; Dynamic nuclear polarization; Magnetic resonance spectroscopy/spectroscopic imaging; Prostate cancer; Branched-chain aminotransferase
资金
- DOD [PC100427]
- NIH [AA018681, AA005965, AA013521-INIA, EB009070, P41 EB015891]
- GE Healthcare
Recent advancements in the field of hyperpolarized C-13 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-C-13]-2-ketoisocaproate ([1-C-13]-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-C-13]-KIC was administered to prostate cancer cell lines, and the conversion of [1-C-13]-KIC to the metabolic product, [1-C-13]-leucine ([1-C-13]-Leu), could be monitored via hyperpolarized C-13 MRS. (C) 2014 Elsevier Inc. All right reserved.
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