TY - JOUR
T1 - The feasibility of assessing branched-chain amino acid metabolism in cellular models of prostate cancer with hyperpolarized [1-13C]-ketoisocaproate
AU - Billingsley, Kelvin L.
AU - Park, Jae Mo
AU - Josan, Sonal
AU - Hurd, Ralph
AU - Mayer, Dirk
AU - Spielman-Sun, Eleanor
AU - Nishimura, Dwight G.
AU - Brooks, James D.
AU - Spielman, Daniel
N1 - Funding Information:
This work was supported by DOD grant PC100427 , NIH grants AA018681 , AA005965 , AA013521-INIA , EB009070 , and P41 EB015891 , and GE Healthcare.
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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.
KW - Branched-chain aminotransferase
KW - Dynamic nuclear polarization
KW - Hyperpolarized carbon-13
KW - Magnetic resonance spectroscopy/spectroscopic imaging
KW - Prostate cancer
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U2 - 10.1016/j.mri.2014.04.015
DO - 10.1016/j.mri.2014.04.015
M3 - Article
C2 - 24907854
AN - SCOPUS:84904039613
SN - 0730-725X
VL - 32
SP - 791
EP - 795
JO - Magnetic Resonance Imaging
JF - Magnetic Resonance Imaging
IS - 7
ER -