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In vivo monitoring of pH, redox status, and glutathione using L‐band EPR for assessment of therapeutic effectiveness in solid tumors
Author(s) -
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.
Publication year - 2012
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.23196
Subject(s) - glutathione , in vivo , extracellular , chemistry , intracellular , mammary tumor , redox , pathology , cancer , biochemistry , breast cancer , medicine , biology , enzyme , microbiology and biotechnology , organic chemistry
Approach for in vivo real‐time assessment of tumor tissue extracellular pH (pH e ), 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 pH e 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 pH e 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, pH e 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 pH e and a difference of about 0.4 pH units between average pH e values in tumor and normal mammary gland. In summary, the developed multifunctional approach allows for in vivo, noninvasive pH e , extracellular redox, and intracellular glutathione content monitoring during investigation of various therapeutic strategies for solid tumors. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.