Billingsley Kelvin L, Park Jae Mo, Josan Sonal, Hurd Ralph, Mayer Dirk, Spielman-Sun Eleanor, Nishimura Dwight G, Brooks James D, Spielman Daniel
Department of Chemistry & Biochemistry, San Francisco State University, San Francisco, CA 94132, USA.
Department of Radiology, Stanford University, Stanford, CA 94305, USA.
Magn Reson Imaging. 2014 Sep;32(7):791-5. doi: 10.1016/j.mri.2014.04.015. Epub 2014 Apr 28.
Recent advancements in the field of hyperpolarized (13)C 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-(13)C]-2-ketoisocaproate ([1-(13)C]-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-(13)C]-KIC was administered to prostate cancer cell lines, and the conversion of [1-(13)C]-KIC to the metabolic product, [1-(13)C]-leucine ([1-(13)C]-Leu), could be monitored via hyperpolarized (13)C MRS.
超极化（13）C磁共振波谱（MRS）领域的最新进展产生了能够对代谢途径进行实时分析的强大技术。这些非侵入性方法在疾病诊断中的应用越来越多，并进一步用于疾病发生和发展的机制研究。我们的目标是使用一种新型分子探针超极化[1-（13）C]-2-酮异己酸（[1-（13）C]-KIC）研究前列腺癌中的支链氨基转移酶（BCAT）活性，并探索支链氨基酸（BCAA）代谢作为生物标志物的潜力。使用传统分光光度法在体外测定了各种前列腺癌来源（人、小鼠前列腺转基因腺癌（TRAMP）小鼠和人细胞系）的BCAT酶活性。这些初步研究表明，在所有前列腺癌模型中均存在低水平的BCAT活性，但相对于健康组织，前列腺癌中的酶水平有显著改变。使用两种细胞模型（PC-3和DU-145）进行了磁共振波谱研究，这两种模型表现出与人类疾病状态相当的BCAA代谢水平。将超极化[1-（13）C]-KIC施用于前列腺癌细胞系，并可通过超极化（13）C MRS监测[1-（13）C]-KIC向代谢产物[1-（13）C]-亮氨酸（[1-（13）C]-Leu）的转化。
