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

被引:74
作者
Bobko, Andrey A. [1 ]
Eubank, Timothy D. [1 ]
Voorhees, Jeffrey L. [1 ]
Efimova, Olga V. [2 ]
Kirilyuk, Igor A. [3 ]
Petryakov, Sergey [2 ]
Trofimiov, Dmitrii G. [4 ]
Marsh, Clay B. [1 ]
Zweier, Jay L. [2 ]
Grigor'ev, Igor A. [3 ]
Samouilov, Alexandre [2 ]
Khramtsov, Valery V. [1 ]
机构
[1] Ohio State Univ, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA
[2] Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Cardiovasc Med, Dept Internal Med, Columbus, OH 43210 USA
[3] Vorozhtsov Inst Organ Chem, Novosibirsk, Russia
[4] Novosibirsk State Univ, Novosibirsk 630090, Russia
关键词
solid tumors; nitroxides; glutathione; redox status; pH; L-Band EPR; PyMT mice; mammary gland; in vivo; QUANTITATIVE-DETERMINATION; SENSITIVE NITROXIDES; EXTRACELLULAR PH; RESONANCE; OXIMETRY; CANCER;
D O I
10.1002/mrm.23196
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
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 protonelectron 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, 2011. (c) 2011 Wiley Periodicals, Inc.
引用
收藏
页码:1827 / 1836
页数:10
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