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Correlations between 31P-NMR spectroscopy and tissue O2 tension measurements in a murine fibrosarcoma
P Vaupel1, P Okunieff, F Kallinowski
1Department of Radiation Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114.
Abstract:
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 less than or equal to 2% of body weight. Tumor pH and bioenergetics were evaluated by 31P nuclear magnetic resonance spectroscopy (31P-MRS), and tumor tissue oxygen tension (pO2) distribution was examined using O2-sensitive needle electrodes. During growth FSaII tumors showed a progressive loss of phosphocreatine (PCr) and nucleoside triphosphate (NTP) with increasing inorganic phosphate (Pi) and phosphomonoester (PME) signals. Ratios for PCr/Pi, PME/Pi, NTP/Pi, and phosphodiester/inorganic phosphate (PDE/Pi) as well as pH determined by 31P-NMR (pHNMR) and the mean tissue pO2 progressively declined as the tumors increased in size. The only relevant ratio increasing with tumor growth was PME/NTP. When the mean tissue pO2 value was plotted against pHNMR, NTP/Pi, PCr/Pi, PME/Pi, and PDE/Pi for tumor groups of similar mean volumes, a highly significant positive correlation was observed. There was a negative correlation between mean tumor tissue pO2 values and PME/NTP. From these results we concluded that 31P-MRS 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 O2-limited energy metabolism. Finally, a correlation between the proportion of pO2 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.
Insights
Investigating tumor growth in mice revealed that declining oxygen levels correlate with altered energy metabolism. This finding is crucial for understanding tumor behavior and optimizing radiation therapy for hypoxic tumors.
Area of Science:
- Oncology
- Biophysics
- Medical Physics
Background:
- Tumor growth leads to metabolic changes affecting treatment efficacy.
- Understanding the relationship between tumor oxygenation and bioenergetics is critical for cancer therapy.
Purpose of the Study:
- To investigate size-dependent metabolic alterations in murine fibrosarcoma (FSaII) tumors.
- To correlate tumor bioenergetics and oxygenation status in vivo.
- To assess the potential of 31P-MRS for evaluating tumor radiobiology.
Main Methods:
- Utilized 31P nuclear magnetic resonance spectroscopy (31P-MRS) to assess tumor pH and bioenergetics.
- Employed O2-sensitive needle electrodes to measure tissue oxygen tension (pO2) distribution.
- Studied conscious mice with FSaII tumors up to 2% of body weight.
Main Results:
- Progressive decline in phosphocreatine (PCr) and nucleoside triphosphate (NTP) with tumor growth.
- Decreased pH, PCr/Pi, NTP/Pi, and mean pO2 observed as tumors enlarged.
- Significant positive correlation found between pO2 and energy metabolites (pH, PCr/Pi, NTP/Pi, PDE/Pi).
Conclusions:
- 31P-MRS can detect bioenergetic changes linked to tumor oxygenation.
- FSaII tumor metabolism is oxygen-limited due to microcirculation issues.
- Hypoxic cell fraction correlates with low pO2, impacting radiation therapy effectiveness.