Fast detection of choline-containing metabolites in liver using 2D 1H-14N three-bond correlation (HN3BC) spectroscopy

Fast detection of choline-containing metabolites in liver using 2D 1H-14N three-bond correlation (HN3BC) spectroscopy
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DOI:
10.1016/j.jmr.2011.11.019
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发表时间:
2012-01-01
影响因子:
2.2
通讯作者:
Liu, Maili
Liu, Maili
中科院分区:
化学3区
文献类型:
--
作者:
Mao, Xi-an;Li, Ning;Liu, Maili

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通过磁共振波谱(MRS)检测和定量组织中的总含胆碱代谢物(CCM)作为癌症的生物标志物受到相当大的关注。组织CCM主要是胆碱(Cho)、磷酸胆碱(PCo)和甘油磷酸胆碱(GPCho)。由于组织CCM的甲基H-1共振在19 H-1 MRS中表现出小的化学位移差异和显著重叠,因此排除了单个组分的定量。能够分辨组织CCM的各个成分的MRS方法的开发将是一个重大的进步。本文中,2D H-1-N-14 HSQC技术的改进靶向于CH 2 O基团中的两个亚甲基H-1((3)J(1H 14 N)= 2.7 Hz),并在生理温度(37 ℃)下应用于离体小鼠和人肝脏样品。具体地说,H1-N-14 HSQC技术被修改为二维H1-N-14三键关联(HN 3BC)实验,该实验选择性地检测CCMs中与N-14偶联的CH 2 O的H-1。来自Cho、PCho和GPCho组分的单独信号以高检测灵敏度被解析。在14.1T下,有效样品体积为0.2ml时,可在1.5min内记录到小鼠肝脏的HN_3BC二维谱,在3 min内记录到人肝癌组织的HN_3BC二维谱。(C)2011 Elsevier Inc. All rights reserved.
Detection and quantification of total choline-containing metabolites (CCMs) in tissues by magnetic resonance spectroscopy (MRS) has received considerable attention as a biomarker of cancer. Tissue CCMs are mainly choline (Cho), phosphocholine (PCho), and glycerophosphocholine (GPCho). Because the methyl H-1 resonances of tissue CCMs exhibit small chemical shift differences and overlap significantly in 19 H-1 MRS, quantification of individual components is precluded. Development of a MRS method capably of resolving individual components of tissue CCMs would be a significant advance. Herein, a modification of the 2D H-1-N-14 HSQC technique is targeted on the two methylene H-1 in the CH2O group ((3)J(1H14N) = 2.7 Hz) and applied to ex vivo mouse and human liver samples at physiological temperature (37 degrees C). Specifically, the H-1-N-14 HSQC technique is modified into a 2D H-1-N-14 three-bond correlation (HN3BC) experiment, which selectively detects the H-1 of CH2O coupled to N-14 in CCMs. Separate signals from Cho, PCho, and GPCho components are resolved with high detection sensitivity. A 2D HN3BC spectrum can be recorded from mouse liver in only 1.5 min and from human carcinoma liver tissue in less than 3 min with effective sample volume of 0.2 ml at 14.1 T. (C) 2011 Elsevier Inc. All rights reserved.