Comparison of relative changes in phosphatic metabolites and phospholipids after irradiation

Measurements of phosphatic metabolites and phospholipids using 31P NMR spectroscopy were performed on tumor extracts at specific times before and after a priming dose of radiation at 32 or 65 Gy. At both doses, statistically significant increases in the high-energy phosphates PCr and ATP, relative to their primary hydrolysis product Pi, were detected at 24 h after irradiation. These spectral changes are consistent with an increased capacity for aerobic metabolism and oxidative phosphorylation. The changes coincide with a significant reduction in the hypoxic cell fraction and 50% tumor control dose measurements reported previously for the same tumor model. A significant increase in the ratio of phosphorylethanolamine to phosphorylcholine was also detected at 24 h. The ratio of ethanolamine-containing to choline-containing phospholipids increased significantly between 48 and 96 h. The spectral changes measured in this study coincide with the changes in the hypoxic state of the tumor after irradiation and are consistent with spectral measurements performed in vivo. The high-resolution spectroscopic data also identify specific metabolites contributing to spectral changes measured in vivo.