Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading.
Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading.
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DOI：
10.1158/0008-5472.can-08-0749
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发表时间：
2008-10-15
期刊：
影响因子：
11.2
通讯作者：
Kurhanewicz J
中科院分区：
文献类型：
--
作者：
Albers MJ;Bok R;Chen AP;Cunningham CH;Zierhut ML;Zhang VY;Kohler SJ;Tropp J;Hurd RE;Yen YF;Nelson SJ;Vigneron DB;Kurhanewicz J
一种使用超极化13 C标记的丙酮酸盐并利用癌症中糖酵解增加的非凡新技术有可能改善磁共振成像用于检测和表征前列腺癌的方式。本研究的目的是首次使用小鼠前列腺转基因腺癌（TRAMP）模型定量测定不同组织学级别前列腺癌之间超极化[1- 13 C]丙酮酸及其代谢产物的差异。使用快速光谱成像技术对正常小鼠和患有低级别和高级别前列腺肿瘤的TRAMP小鼠的整个腹部的乳酸盐、丙氨酸盐和总超极化碳（THC =乳酸盐+丙酮酸盐+丙氨酸盐）进行成像。在1周内，解剖小鼠并对肿瘤进行组织学分析。超极化乳酸SNR水平随着癌症的发展和进展而显著增加（P < 0.05）（正常前列腺、低级别原发性肿瘤和高级别原发性肿瘤分别为41 ± 11、74 ± 17和154 ± 24），与组织学分级的相关系数为0.95。此外，三组之间乳酸水平的重叠很小，七个正常前列腺中只有一个与低级别原发性肿瘤重叠。THC（一种可能的底物摄取测量）和超极化丙氨酸的量也随肿瘤分级而增加，但组间重叠较多。总之，升高的超极化乳酸盐和潜在的THC和丙氨酸是前列腺癌存在和组织学分级的非侵入性生物标志物，可用于前列腺癌患者的未来三维13 C光谱成像研究。
An extraordinary new technique using hyperpolarized 13C-labeled pyruvate and taking advantage of increased glycolysis in cancer has the potential to improve the way magnetic resonance imaging is used for detection and characterization of prostate cancer. The aim of this study was to quantify, for the first time, differences in hyperpolarized [1-13C] pyruvate and its metabolic products between the various histologic grades of prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Fast spectroscopic imaging techniques were used to image lactate, alanine, and total hyperpolarized carbon (THC = lactate + pyruvate + alanine) from the entire abdomen of normal mice and TRAMP mice with low- and high-grade prostate tumors in 14 s. Within 1 week, the mice were dissected and the tumors were histologically analyzed. Hyperpolarized lactate SNR levels significantly increased (P < 0.05) with cancer development and progression (41 ± 11, 74 ± 17, and 154 ± 24 in normal prostates, low-grade primary tumors, and high-grade primary tumors, respectively) and had a correlation coefficient of 0.95 with the histologic grade. In addition, there was minimal overlap in the lactate levels between the three groups with only one of the seven normal prostates overlapping with the low-grade primary tumors. The amount of THC, a possible measure of substrate uptake, and hyperpolarized alanine also increased with tumor grade but showed more overlap between the groups. In summary, elevated hyperpolarized lactate and potentially THC and alanine are noninvasive biomarkers of prostate cancer presence and histologic grade that could be used in future three-dimensional 13C spectroscopic imaging studies of prostate cancer patients.