Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
NMR Biomed. 2020 May;33(5):e4269. doi: 10.1002/nbm.4269. Epub 2020 Mar 4.
Hyperpolarized (HP) MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since -lactate signal levels obtained from HP imaging depend on multiple factors, such as the rate of substrate delivery via the vasculature, the expression level of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH), and the local lactate pool size, the interpretation of HP metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.e., NMR isotopomer analysis, western blot analysis) derived from an MDA-MB-231 xenograft model in nude rats were used to test for correlations between the in vivo data and the ex vivo measures. The lactate-to-pyruvate ratio from HP MRI was strongly correlated with [1- ]lactate concentration measured from the extracts using NMR (R = 0.69, p 0.05), as well as negatively correlated with tumour wet weight (R = 0.60, p 0.05). In this tumour model, both MCT1 and MCT4 expressions were positively correlated with wet weight ( = 0.78 and 0.93, respectively, p 0.01). Lactate pool size and the lactate-to-pyruvate ratio were not significantly correlated.
高极化（HP）MRI 提供了一种非侵入性监测肿瘤内乳酸代谢的方法。由于 HP 成像获得的 - 乳酸信号水平取决于多种因素，如通过血管输送底物的速率、单羧酸转运蛋白（MCT）和乳酸脱氢酶（LDH）的表达水平以及局部乳酸池大小，因此 HP 代谢图像的解释仍然具有挑战性。在这项研究中，从裸鼠 MDA-MB-231 异种移植模型的离体组织提取物测量（即 NMR 同位素分析、western blot 分析）用于测试体内数据与离体测量之间的相关性。HP MRI 获得的乳酸/丙酮酸比值与使用 NMR 从提取物中测量的 [1-] 乳酸浓度强烈相关（R = 0.69，p 0.05），并且与肿瘤湿重呈负相关（R = -0.60，p 0.05）。在该肿瘤模型中，MCT1 和 MCT4 的表达均与湿重呈正相关（分别为 r = 0.78 和 0.93，p 0.01）。乳酸池大小和乳酸/丙酮酸比值之间没有显著相关性。
