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 Full article

Journal

Magnetic Resonance in Medicine
ISSN: 0740-3194

Output data

Year: 2012, Volume: 67, Number: 6, Pages: 1827-1836 Pages count : DOI: 10.1002/mrm.23196

Tags

solid tumors; nitroxides; glutathione; redox status; pH; L-Band EPR; PyMT mice; mammary gland; in vivo

Authors

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

Affiliations

1	(Данные Web of science) Ohio State Univ, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA
2	(Данные Web of science) Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Cardiovasc Med, Dept Internal Med, Columbus, OH 43210 USA
3	(Данные Web of science) Vorozhtsov Inst Organ Chem, Novosibirsk, Russia
4	(Данные Web of science) Novosibirsk State Univ, Novosibirsk 630090, Russia

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.

Bobko A.A. , Eubank T.D. , Voorhees J.L. , Efimova O.V. , Kirilyuk I.A. , Petryakov S. , Trofimiov D.G. , Marsh C.B. , Zweier J.L. , Grigor'ev I.A. , Samouilov A. , Khramtsov V.V.
In vivo monitoring of pH, redox status, and glutathione using L-band EPR for assessment of therapeutic effectiveness in solid tumors

Magnetic Resonance in Medicine. 2012. V.67. N6. P.1827-1836. DOI: 10.1002/mrm.23196 WOS Scopus РИНЦ OpenAlex

Full text from publisher

Published online:	Nov 23, 2011
Published print:	Jun 1, 2012

Web of science:	WOS:000304086000036
Scopus:	2-s2.0-84861018075
Elibrary:	17985216
OpenAlex:	W2072480297

DB	Citing
Web of science	75
Scopus	79
Elibrary	76
OpenAlex	86