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Media type:
E-Article
Title:
Correlations between31P- NMR Spectroscopy and Tissue O2Tension Measurements in a Murine Fibrosarcoma
Contributor:
Vaupel, Peter;
Okunieff, Paul;
Kallinowski, Friedrich;
Neuringer, Leo J.
imprint:
Academic Press, Inc., 1989
Published in:Radiation Research
Language:
English
ISSN:
0033-7587;
1938-5404
Origination:
Footnote:
Description:
<p> Size-dependent changes in therapeutically relevant and interrelated metabolic parameters of a murine fibrosarcoma (FSaII) were investigated in vivo using conscious (unanesthetized) animals and tumor sizes ≤ 2% of body weight. Tumor pH and bioenergetics were evaluated by<sup>31</sup>P nuclear magnetic resonance spectroscopy (<tex-math>${}^{31}{\rm P}\text{-}{\rm MRS}$</tex-math>), and tumor tissue oxygen tension (<tex-math>$p{\rm O}_{2}$</tex-math>) distribution was examined using<tex-math>${\rm O}_{2}\text{-sensitive}$</tex-math>needle electrodes. During growth FSaII tumors showed a progressive loss of phosphocreatine (PCr) and nucleoside triphosphate (NTP) with increasing inorganic phosphate (<tex-math>$P_{{\rm i}}$</tex-math>) and phosphomonoester (PME) signals. Ratios for<tex-math>${\rm PCr}/P_{{\rm i}}$</tex-math>,<tex-math>${\rm PME}/P_{{\rm i}},\ {\rm NTP}/P_{{\rm i}}$</tex-math>, and phosphodiester/inorganic phosphate (<tex-math>${\rm PDE}/P_{{\rm i}}$</tex-math>) as well as pH determined by<tex-math>${}^{31}{\rm P}\text{-}{\rm NMR}\ ({\rm pH}_{{\rm NMR}})$</tex-math>and the mean tissue<tex-math>$p{\rm O}_{2}$</tex-math>progressively declined as the tumors increased in size. The only relevant ratio increasing with tumor growth was PME/NTP. When the mean tissue<tex-math>$p{\rm O}_{2}$</tex-math>value was plotted against<tex-math>${\rm pH}_{{\rm NMR}},\ {\rm NTP}/P_{{\rm i}},\ {\rm PCr}/P_{{\rm i}},\ {\rm PME}/P_{{\rm i}}$</tex-math>, and<tex-math>${\rm PDE}/P_{{\rm i}}$</tex-math>for tumor groups of similar mean volumes, a highly significant positive correlation was observed. There was a negative correlation between mean tumor tissue<tex-math>$p{\rm O}_{2}$</tex-math>values and PME/NTP. From these results we concluded that<tex-math>${}^{31}{\rm P}\text{-}{\rm MRS}$</tex-math>can detect changes in tumor bioenergetics brought about by changes in tumor oxygenation. Furthermore, the close correlation between oxygenation and energy status suggests that the microcirculation in FSaII tumors yields an<tex-math>${\rm O}_{2}\text{-limited}$</tex-math>energy metabolism. Finally, a correlation between the proportion of<tex-math>$p{\rm O}_{2}$</tex-math>readings between 0 and 2.5 mmHg and the radiobiologically hypoxic cell fraction in FSaII tumors was observed. The latter finding might be of particular importance for radiation therapy. </p>