三种氘标记的葡萄糖在大鼠脑胶质瘤细胞中的代谢特征对比
收稿日期: 2023-01-03
网络出版日期: 2023-03-23
基金资助
广东省自然科学基金资助项目(2022B1515120068);广东省自然科学基金资助项目(2020B1212060051);中国科学院全球共性挑战专项(321GJHZ2022081GC);国家重点研发计划资助项目(2022YFA1004203);国家重点研发计划资助项目(2021YFE0204400);国家重点研发计划资助项目(2021YFF0501500);中国科学院青促会基金(Y2021098);深圳市基础研究计划资助项目(JCY20200109110612375)
Comparison Study of the Metabolic Characteristics of Three Kinds of Deuterium-labeled Glucose in Rat Glioma Cells
Received date: 2023-01-03
Online published: 2023-03-23
磁共振氘（2H）成像是近年来涌现出的一种能在活体水平下实现特定代谢通路可视化的分子代谢成像方法，在癌症检测等重大疾病方面具有极好的临床应用前景．本文分析了三种不同氘标记葡萄糖——[6,6’-2H2]-葡萄糖、[2,3,4,6,6’-2H5]-葡萄糖和[1,2,3,4,5,6,6’-2H7]-葡萄糖在脑胶质瘤细胞中的代谢特征差异．将大鼠脑胶质瘤C6细胞与三种氘标记的葡萄糖一起孵育，收集不同时刻细胞培养基样品，采用核磁共振波谱仪对样品进行核磁共振氘谱采集，获取不同时间三种氘标记葡萄糖的消耗量以及下游代谢产物水和乳酸的产量，从而得出三种氘标记葡萄糖探针在肿瘤细胞中的消耗速度以及代谢物的生成速度等动态代谢特征．结果显示在细胞实验中三种氘标记葡萄糖均能够显示出肿瘤细胞的代谢特征，且葡萄糖的消耗速度并无显著性差异，氘标记水和氘标记乳酸的产量也符合理论估算．因此本文认为低成本的氘标记葡萄糖探针[2,3,4,6,6’-2H5]-葡萄糖具备更好的临床转化价值．
方羿 , 万倩 , 袁家文 , 林绍强 , 李烨 , 刘新 , 郑海荣 , 邹超 . 三种氘标记的葡萄糖在大鼠脑胶质瘤细胞中的代谢特征对比[J]. 波谱学杂志, 2023 , 40(3) : 239 -245 . DOI: 10.11938/cjmr20233048
Deuterium (2H) magnetic resonance imaging is an emerging molecular metabolic imaging method that can visualize the metabolic pathway in vivo, and therefore has great potential in clinical applications such as cancer detection. In this work, we aimed to compare the metabolic characteristics of three different deuterium-labeled glucose, namely [6,6’-2H2]-glucose, [2,3,4,6,6’-2H5]-glucose, and [1,2,3,4,5,6,6’-2H7]-glucose through glioma cell experiment. The rat glioma C6 cells were incubated with three deuterium-labeled glucose, and cell media samples were collected at different time points, and underwent magnetic resonance deuterium spectroscopy to obtain the glucose consumption and the production of downstream metabolites, such as water and lactate, at each time point. The results showed that all three kinds of deuterium-labeled glucose probes were able to demonstrate the characteristic of tumor metabolism, and there was no significant difference in the consumption rate of the three kinds of deuterium-labeled glucose probes, and the production of the deuterium-labeled water and deuterium-labeled lactate were consistent with the theoretical estimation. Therefore, this paper concludes that the cost-effective deuterium-labeled glucose probe [2,3,4,6,6’-2H5]-glucose has great clinical translational values.
| [1] | DING H, HAROON A, WAN S, et al. Old discovery leading to new era: metabolic imaging of cancer with deuterium MRI[J]. Magnetochemistry, 2022, 9(1): 6. |
| [2] | ZHANG Y, LOU F Y, FANG K, et al. Review of a new molecular imaging method—deuterium metabolic spectroscopy and imaging[J]. Chinese J Magn Reson, 2022, 39(3): 356-365. |
| [2] | 张怡, 楼飞洋, 方可, 等. 分子影像新技术—氘代谢波谱及成像的综述与展望[J]. 波谱学杂志, 2022, 39(3): 356-365. |
| [3] | YUAN J, CHAO ZOU, YE Q, et al. A review of advances in magnetic resonance deuterium metabolic imaging research[J]. Life Science Instruments, 2022, 20(1): 4-16. |
| [3] | 袁家文, 邹超, 叶琼, 等. 磁共振氘代谢成像研究进展综述[J]. 生命科学仪器, 2022, 20(1): 4-16. |
| [4] | UREY H C, BRICKWEDDE F G, MURPHY G M. A hydrogen isotope of mass 2 and its concentration[J]. Phys Rev, 1932, 40(1): 1-15. |
| [5] | SUN X Y. 2H NMR study of deuterium distribution in molecule[J]. Chinese J Magn Reson, 1985, 2(2): 121-124. |
| [5] | 孙贤育. 2H NMR研究分子中氢同位素氘分布[J]. 波谱学杂志, 1985, 2(2): 121-124. |
| [6] | RUHM L, AVDIEVICH N, ZIEGS T, et al. Deuterium metabolic imaging in the human brain at 9.4 Tesla with high spatial and temporal resolution[J]. Neuroimage, 2021, 244: 118639. |
| [7] | VAN DE WEIJER T, SCHRAUWEN-HINDERLING V B. Application of magnetic resonance spectroscopy in metabolic research[J]. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(4): 741-748. |
| [8] | SERKOVA N J, BROWN M S. Quantitative analysis in magnetic resonance spectroscopy: from metabolic profiling to in vivo biomarkers[J]. Bioanalysis, 2012, 4(3): 321-341. |
| [9] | DE FEYTER H M, DE GRAAF R A. Deuterium metabolic imaging - Back to the future[J]. J Magn Reson, 2021, 326: 106932. |
| [10] | LU M, ZHU X H, ZHANG Y, et al. Quantitative assessment of brain glucose metabolic rates using in vivo deuterium magnetic resonance spectroscopy[J]. J Cereb Blood Flow Metab, 2017, 37(11): 3518-3530. |
| [11] | DE FEYTER H M, BEHAR K L, CORBIN Z A, et al. Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo[J]. Sci Adv, 2018, 4(8): eaat7314. |
| [12] | STRAATHOF M, MEERWALDT A E, DE FEYTER H M, et al. Deuterium metabolic imaging of the healthy and diseased brain[J]. Neuroscience, 2021, 474: 94-99. |
| [13] | HESSE F, SOMAI V, KREIS F, et al. Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging[J]. Proc Natl Acad Sci, 2021, 118(12): e2014631118. |
| [14] | KREIS F, WRIGHT A J, HESSE F, et al. Measuring tumor glycolytic flux in vivo by using fast deuterium MRI[J]. Radiology, 2020, 294(2): 289-296. |
| [15] | MAHAR R, ZENG H, GIACALONE A, et al. Deuterated water imaging of the rat brain following metabolism of [2H7]glucose[J]. Magn Reson Med, 2021, 85(6): 3049-3059. |
| [16] | MARTíNEZ-REYES I, CHANDEL N S. Mitochondrial TCA cycle metabolites control physiology and disease[J]. Nat Commun, 2020, 11(1): 102. |
| [17] | VANDER HEIDEN M G, CANTLEY L C, THOMPSON C B. Understanding the Warburg effect: the metabolic requirements of cell proliferation[J]. Science, 2009, 324(5930): 1029-1033. |
| [18] | SIM?ES R V, HENRIQUES R N, CARDOSO B M, et al. Glucose fluxes in glycolytic and oxidative pathways detected in vivo by deuterium magnetic resonance spectroscopy reflect proliferation in mouse glioblastoma[J]. Neuroimage Clin, 2022, 33: 102932. |
| [19] | DE FEYTER H M, THOMAS M A, BEHAR K L, et al. NMR visibility of deuterium-labeled liver glycogen in vivo[J]. Magn Reson Med, 2021, 86(1): 62-68. |
| [20] | KAGGIE J D, KHAN A S, MATYS T, et al. Deuterium metabolic imaging and hyperpolarized13C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism[J]. Neuroimage, 2022, 257: 119284. |
| [21] | PETERS D C, MARKOVIC S, BAO Q, et al. Improving deuterium metabolic imaging (DMI) signal-to-noise ratio by spectroscopic multi-echo bSSFP: A pancreatic cancer investigation[J]. Magn Reson Med, 2021, 86(5): 2604-2617. |
| [22] | VELTIEN A, VAN ASTEN J, RAVICHANDRAN N, et al. Simultaneous recording of the uptake and conversion of glucose and choline in tumors by deuterium metabolic imaging[J]. Cancers (Basel), 2021, 13(16): 4034. |
| [23] | MAHAR R, DONABEDIAN P L, MERRITT M E. HDO production from [2H7]glucose quantitatively identifies Warburg metabolism[J]. Sci Rep, 2020, 10(1): 8885. |
| [24] | MAHAR R, CHANG M C, MERRITT M E. Measuring NQO1 bioactivation using [2H7]glucose[J]. Cancers (Basel), 2021, 13(16): 4165. |
| [25] | FLATT E, LANZ B, PILLOUD Y, et al. Measuring glycolytic activity with hyperpolarized [2H7, U-13C6] D-glucose in the naive mouse brain under different anesthetic conditions[J]. Metabolites, 2021, 11(7): 413. |
| [26] | ZOU C, RUAN Y, LI H, et al. A new deuterium-labeled compound [2,3,4,6,6’-2H5]-D-glucose for deuterium magnetic resonance metabolic imaging[J]. NMR Biomed, 2022: e4890. |
| [27] | PéRONNET F, MIGNAULT D, DU SOUICH P, et al. Pharmacokinetic analysis of absorption, distribution and disappearance of ingested water labeled with D?O in humans[J]. Eur J Appl Physiol, 2012, 112(6): 2213-2222. |
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