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

Andrey A. Bobko, Timothy D. Eubank, Jeffrey L. Voorhees, Olga V. Efimova, Igor A. Kirilyuk, Sergey Petryakov, Dmitrii G. Trofimiov, Clay B. Marsh, Jay L. Zweier, Igor A. Grigor'Ev, Alexandre Samouilov, Valery V. Khramtsov

Research output: Contribution to journalArticlepeer-review

Abstract

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 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 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.

Original languageEnglish (US)
Pages (from-to)1827-1836
Number of pages10
JournalMagnetic Resonance in Medicine
Volume67
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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