Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
Magn Reson Med. 2010 Apr;63(4):872-80. doi: 10.1002/mrm.22276.
Measurements of the conversion of hyperpolarized [1-(13)C]pyruvate into lactate, in the reaction catalyzed by lactate dehydrogenase, have shown promise as a metabolic marker for the presence of disease and response to treatment. However, it is unclear whether this represents net flux of label from pyruvate to lactate or exchange of isotope between metabolites that are close to chemical equilibrium. Using saturation and inversion transfer experiments, we show that there is significant exchange of label between lactate and pyruvate in a murine lymphoma in vivo. The rate constants estimated from the magnetization transfer experiments, at specific points during the time course of label exchange, were similar to those obtained by fitting the changes in peak intensities during the entire exchange time course to a kinetic model for two-site exchange. These magnetization transfer experiments may therefore provide an alternative and more rapid way of estimating flux between pyruvate and lactate to serial measurements of pyruvate and lactate (13)C peak intensities following injection of hyperpolarized [1-(13)C]pyruvate.
对乳酸脱氢酶催化的[1-(13)C]丙酮酸转化为乳酸的测量,已经显示出作为存在疾病和对治疗反应的代谢标志物的潜力。然而,目前尚不清楚这是否代表来自丙酮酸的标记物的净通量到乳酸或代谢物之间的同位素交换,这些代谢物接近化学平衡。使用饱和和反转转移实验,我们表明在体内鼠淋巴瘤中有显著的标记物在乳酸和丙酮酸之间的交换。在标记物交换过程中的特定时间点从磁化转移实验估计的速率常数,与通过将整个交换时间过程中的峰强度变化拟合到双位点交换的动力学模型来获得的那些相似。因此,这些磁化转移实验可以提供一种替代的、更快速的方法来估计丙酮酸和乳酸之间的通量,以在注射[1-(13)C]丙酮酸后对丙酮酸和乳酸(13C)峰强度进行连续测量。