title: In vivo monitoring of pH, redox status, and glutathione using L-band EPR for assessment of therapeutic effectiveness in solid tumors.
abstract: 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.
authors: Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors: Andrey A
authors: AA
authors: Bobko
authors: Timothy D
authors: TD
authors: Eubank
authors: Jeffrey L
authors: JL
authors: Voorhees
authors: Olga V
authors: OV
authors: Efimova
authors: Igor A
authors: IA
authors: Kirilyuk
authors: Sergey
authors: S
authors: Petryakov
authors: Dmitrii G
authors: DG
authors: Trofimiov
authors: Clay B
authors: CB
authors: Marsh
authors: Jay L
authors: JL
authors: Zweier
authors: Igor A
authors: IA
authors: Grigor'ev
authors: Alexandre
authors: A
authors: Samouilov
authors: Valery V
authors: VV
authors: Khramtsov
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D005978:Glutathione / Q000032:analysis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D010084:Oxidation-Reduction; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005978:Glutathione