Relationship of changes in pH and energy status to hypoxic cell fraction and hyperthermia sensitivity

The relative concentrations of nucleotide triphosphates, creatine phosphate, inorganic phosphate, and pH have been evaluated as a function of tumor volume in a murine fibrosarcoma (FSaII) by ³¹P NMR spectroscopy. As the tumor volume increased from 60-1250 mm³, the ratio of phosphocreatine to inorganic phosphate systemically decreased. This decrease paralleled a decrease in the ratio of nucleotide triphosphate to inorganic phosphate in thesame tumor volume range. The tumor pH as measured by ³¹P NMR decreased slightly with tumor growth. A pH of 7.17 ± 0.07 (n = 17) was found for tumors between 60 and 150 mm³, whereas for tumors greater than 900 mm³, a pH of 7.05 ± .03 (n = 6) was noted. Intermediate size tumors (151-900) had a pH of 7.12 ± 0.09 (n = 18). The change in tumor energy status with tumor volume inversely paralleled the change in tumor radiobiologic hypoxic cell fraction and suggested a causal relationship between tumor nutrient status and energy status. Tumor thermal sensitivity also increased with tumor volume, suggesting a relationship between pH, energy status, and thermal sensitivity, as has been demonstrated under in vitro conditions. Each NMR parameter was found to correlate significantly with tumor volume independent of the other NMR parameters.