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 language | English (US) |
|---|---|
| Pages (from-to) | 1827-1836 |
| Number of pages | 10 |
| Journal | Magnetic Resonance in Medicine |
| Volume | 67 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2012 |
| Externally published | Yes |
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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
Cite this
In vivo monitoring of pH, redox status, and glutathione using L-band EPR for assessment of therapeutic effectiveness in solid tumors. / 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.
In: Magnetic Resonance in Medicine, Vol. 67, No. 6, 06.2012, p. 1827-1836.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vivo monitoring of pH, redox status, and glutathione using L-band EPR for assessment of therapeutic effectiveness in solid tumors
AU - Bobko, Andrey A.
AU - Eubank, Timothy D.
AU - Voorhees, Jeffrey L.
AU - Efimova, Olga V.
AU - Kirilyuk, Igor A.
AU - Petryakov, Sergey
AU - Trofimiov, Dmitrii G.
AU - Marsh, Clay B.
AU - Zweier, Jay L.
AU - Grigor'Ev, Igor A.
AU - Samouilov, Alexandre
AU - Khramtsov, Valery V.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - glutathione
KW - in vivo
KW - L-Band EPR
KW - mammary gland
KW - nitroxides
KW - pH
KW - PyMT mice
KW - redox status
KW - solid tumors
UR - http://www.scopus.com/inward/record.url?scp=84861018075&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861018075&partnerID=8YFLogxK
U2 - 10.1002/mrm.23196
DO - 10.1002/mrm.23196
M3 - Article
C2 - 22113626
AN - SCOPUS:84861018075
VL - 67
SP - 1827
EP - 1836
JO - Magnetic Resonance in Medicine
JF - Magnetic Resonance in Medicine
SN - 0740-3194
IS - 6
ER -