Imaging of pH in vivo using hyperpolarized (13)C-labelled zymonic acid.
Imaging of pH in vivo using hyperpolarized (13)C-labelled zymonic acid.
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DOI：
10.1038/ncomms15126
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发表时间：
2017-05-11
影响因子：
16.6
通讯作者：
Schilling F
中科院分区：
文献类型：
--
作者：
Düwel S;Hundshammer C;Gersch M;Feuerecker B;Steiger K;Buck A;Walch A;Haase A;Glaser SJ;Schwaiger M;Schilling F
在癌症、炎症和缺血等病理过程中，自然pH调节机制可能被推翻，导致人体局部pH值发生变化。本文证明了13c标记的酶酸（ZA）可以用作超极化磁共振pH成像传感器。ZA是由[1-13C]丙酮酸合成的，其13C共振频率高达3.0 p.m。每个pH单位在生理pH范围内。超极化信号增强的长寿命可以监测pH值，不受浓度、温度、离子强度和蛋白质浓度的影响。我们展示了大鼠肾脏和皮下接种的乳腺腺癌细胞系肿瘤的体内pH图，并将ZA描述为主要存在于细胞外空间的无毒化合物。我们认为ZA是一种可靠的、无创的细胞外成像传感器，可以定位和量化pH值，有可能提高对以异常酸碱平衡为特征的疾病的理解、诊断和治疗。局部pH值改变可能是癌症、炎症和缺血等病理的表现。在这里，d<s:1> well等人展示了超极化13c标记的酶酸可以作为一种非侵入性探针来绘制和测量体内的pH值，这表明它是临床成像和诊断工具的候选物。
Natural pH regulatory mechanisms can be overruled during several pathologies such as cancer, inflammation and ischaemia, leading to local pH changes in the human body. Here we demonstrate that 13C-labelled zymonic acid (ZA) can be used as hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1-13C]pyruvic acid and its 13C resonance frequencies shift up to 3.0 p.p.m. per pH unit in the physiological pH range. The long lifetime of the hyperpolarized signal enhancement enables monitoring of pH, independent of concentration, temperature, ionic strength and protein concentration. We show in vivo pH maps within rat kidneys and subcutaneously inoculated tumours derived from a mammary adenocarcinoma cell line and characterize ZA as non-toxic compound predominantly present in the extracellular space. We suggest that ZA represents a reliable and non-invasive extracellular imaging sensor to localize and quantify pH, with the potential to improve understanding, diagnosis and therapy of diseases characterized by aberrant acid-base balance. Local pH alterations can be manifestations of pathologies such as cancer, inflammation and ischaemia. Here Düwel et al. show hyperpolarized 13C-labelled zymonic acid can be used as a non-invasive probe to map and measure pH in vivo, suggesting it as a candidate for clinical imaging and a diagnostic tool.