Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle-upon-Tyne, UK.
NMR Biomed. 2012 Feb;25(2):271-8. doi: 10.1002/nbm.1745. Epub 2011 Jul 12.
The metabolism of glycine into glutathione was monitored noninvasively in vivo in intact rat mammary adenocarcinomas (R3230Ac) by MRI and MRS. Metabolism was tracked by following the isotope label from intravenously infused [2-(13)C]-glycine into the glycinyl residue of glutathione. Signals from [2-(13)C]-glycine and γ-glutamylcysteinyl-[2-(13)C]-glycine ((13)C-glutathione) were detected by nonlocalized (13)C spectroscopy, as these resonances are distinct from background signals. In addition, using spectroscopic imaging methods, heterogeneity in the in vivo tumor distribution of glutathione was observed. In vivo spectroscopy also detected isotope incorporation from [2-(13)C]-glycine into both the 2- and 3-carbons of serine. Analyses of tumor tissue extracts showed single- and multiple-label incorporation from [2-(13)C]-glycine into serine from metabolism through the serine hydroxymethyltransferase and glycine cleavage system pathways. Mass spectrometric analysis of extracts also showed that isotope-labeled serine is further metabolized via the trans-sulfuration pathway, as (13)C isotope labels appear in both the glycinyl and cysteinyl residues of glutathione. Our studies demonstrate the use of MRI and MRS for the monitoring of tumor metabolic processes central to oxidative stress defense.
我们通过 MRI 和 MRS 技术，在体无创监测了完整的大鼠乳腺腺癌（R3230Ac）中甘氨酸向谷胱甘肽代谢的过程。通过静脉内输注的[2-(13)C]-甘氨酸追踪同位素标记，进入谷胱甘肽的甘氨酰残基，从而跟踪代谢过程。通过非局部（13)C 光谱学可以检测到[2-(13)C]-甘氨酸和γ-谷氨酰半胱氨酸-[2-(13)C]-甘氨酸（(13)C-谷胱甘肽）的信号，因为这些共振与背景信号不同。此外，使用光谱成像方法，观察到了谷胱甘肽在体内肿瘤分布的异质性。体内光谱还检测到了[2-(13)C]-甘氨酸掺入丝氨酸的 2-和 3-位碳的同位素。对肿瘤组织提取物的分析表明，通过丝氨酸羟甲基转移酶和甘氨酸裂解系统途径，[2-(13)C]-甘氨酸单一和多次掺入丝氨酸。提取物的质谱分析还表明，标记的丝氨酸进一步通过转硫途径代谢，因为（13)C 同位素标记出现在谷胱甘肽的甘氨酰和半胱氨酰残基中。我们的研究证明了 MRI 和 MRS 可用于监测与氧化应激防御相关的肿瘤代谢过程。
