Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1,2-13C2]pyruvate in vivo
Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1,2-13C2]pyruvate in vivo
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DOI：
10.1002/nbm.1749
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发表时间：
2012-02-01
影响因子：
2.9
通讯作者：
Cunningham, Charles H.
中科院分区：
文献类型：
--
作者：
Chen, Albert P.;Hurd, Ralph E.;Cunningham, Charles H.
对预极化[1-C-13]丙酮酸灌注后的离体和体内心脏进行的C-13 MR波谱研究表明，可以无创监测丙酮酸脱氢酶（PDH）通量的变化。然而，为了研究克雷布斯循环代谢，必须将C-13标记置于丙酮酸的C2位置。因此，利用C1或C2标记的预极化丙酮酸作为示踪剂只能提供健康和疾病中心脏丙酮酸代谢的部分视图。如果在C1和C2位置标记预极化的丙酮酸分子，则可以观察到下游代谢物，其是单剂量试剂的PDH通量（（CO2）-C-13和（HCO 3-）-C-13）和克雷布斯循环通量（[5-C-13]谷氨酸）的结果。在相同的实验中也可以监测心脏pH值，但是在体内可能难以获得（CO2）-C-13共振的足够SNR。使用交错选择性RF脉冲采集方案来改善（CO2）-C-13检测，在体内证明了使用双标记超极化[1，2-C-13（2）]丙酮酸盐作为动态心脏代谢MRS研究的底物以允许同时研究PDH通量、Krebs循环通量和pH的可行性。版权所有（C）2011约翰威利父子有限公司
C-13 MR spectroscopy studies performed on hearts ex vivo and in vivo following perfusion of prepolarized [1-C-13]pyruvate have shown that changes in pyruvate dehydrogenase (PDH) flux may be monitored non-invasively. However, to allow investigation of Krebs cycle metabolism, the C-13 label must be placed on the C2 position of pyruvate. Thus, the utilization of either C1 or C2 labeled prepolarized pyruvate as a tracer can only afford a partial view of cardiac pyruvate metabolism in health and disease. If the prepolarized pyruvate molecules were labeled at both C1 and C2 positions, then it would be possible to observe the downstream metabolites that were the results of both PDH flux ((CO2)-C-13 and (HCO3-)-C-13) and Krebs cycle flux ([5-C-13] glutamate) with a single dose of the agent. Cardiac pH could also be monitored in the same experiment, but adequate SNR of the (CO2)-C-13 resonance may be difficult to obtain in vivo. Using an interleaved selective RF pulse acquisition scheme to improve (CO2)-C-13 detection, the feasibility of using dual-labeled hyperpolarized [1,2-C-13(2)]pyruvate as a substrate for dynamic cardiac metabolic MRS studies to allow simultaneous investigation of PDH flux, Krebs cycle flux and pH, was demonstrated in vivo. Copyright (C) 2011 John Wiley & Sons, Ltd.