In vivo monitoring of pH, redox status, and glutathione using L-band EPR for assessment of therapeutic effectiveness in solid tumors.

In vivo monitoring of pH, redox status, and glutathione using L-band EPR for assessment of therapeutic effectiveness in solid tumors.
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DOI:
10.1002/mrm.23196
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发表时间:
2012-06
影响因子:
3.3
通讯作者:
Khramtsov, Valery V.
Khramtsov, Valery V.
中科院分区:
医学3区
文献类型:
--
作者:
Bobko, Andrey A.;Eubank, Timothy D.;Voorhees, Jeffrey L.;Efimova, Olga V.;Kirilyuk, Igor A.;Petryakov, Sergey;Trofimiov, Dmitrii G.;Marsh, Clay B.;Zweier, Jay L.;Grigor'ev, Igor A.;Samouilov, Alexandre;Khramtsov, Valery V.

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本文介绍了一种基于L-带EPR光谱技术,利用双功能pH和氧化还原氮氧探针和二硫氮氧双自由基,在体内实时检测肿瘤组织细胞外pH值(pHe)、氧化还原和细胞内谷胱甘肽的方法。在用粒细胞巨噬细胞集落刺激因子治疗期间,在携带乳腺癌肿瘤的PyMT小鼠中监测这些参数。观察到肿瘤pHe比正常乳腺组织低约0.4pH单位。与PBS对照治疗相比,粒细胞巨噬细胞集落刺激因子治疗使pH值降低0.3个单位。与正常乳腺组织相比,肿瘤组织还原能力和细胞内谷胱甘肽升高。粒细胞巨噬细胞集落刺激因子治疗导致肿瘤组织还原能力和细胞内谷胱甘肽含量的降低。除了光谱研究,pH值映射进行使用最近提出的可变频率质子-电子双共振成像。与MRI图像叠加的pH标测支持乳腺/肿瘤组织中的探针定位,显示肿瘤组织pHe的高度异质性以及肿瘤和正常乳腺中平均pHe值之间约0.4 pH单位的差异。总之,开发的多功能方法允许在实体瘤的各种治疗策略的研究期间进行体内、非侵入性pH、细胞外氧化还原和细胞内谷胱甘肽含量监测。Magn Reson Med 000:000-000,2011。
Approach for in vivo real-time assessment of tumor tissue extracellular pH (pHe), redox, and intracellular glutathione based on L-band EPR spectroscopy using dual function pH and redox nitroxide probe and disulfide nitroxide biradical, is described. These parameters were monitored in PyMT mice bearing breast cancer tumors during treatment with granulocyte macrophage colony-stimulating factor. It was observed that tumor pHe is about 0.4 pH units lower than that in normal mammary gland tissue. Treatment with granulocyte macrophage colony-stimulating factor decreased the value of pHe by 0.3 units compared with PBS control treatment. Tumor tissue reducing capacity and intracellular glutathione were elevated compared with normal mammary gland tissue. Granulocyte macrophage colony-stimulating factor treatment resulted in a decrease of the tumor tissue reducing capacity and intracellular glutathione content. In addition to spectroscopic studies, pHe mapping was performed using recently proposed variable frequency proton–electron double-resonance imaging. The pH mapping superimposed with MRI image supports probe localization in mammary gland/tumor tissue, shows high heterogeneity of tumor tissue pHe and a difference of about 0.4 pH units between average pHe values in tumor and normal mammary gland. In summary, the developed multifunctional approach allows for in vivo, noninvasive pHe, extracellular redox, and intracellular glutathione content monitoring during investigation of various therapeutic strategies for solid tumors. Magn Reson Med 000:000–000, 2011.
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