31P NMR spectroscopy can predict the optimum interval between fractionated irradiation doses

This study was performed to clarify whether changes in the metabolites observed by phosphorous-31 magnetic resonance spectroscopy (31P-MRS) could indicate an optimum interval between two doses of radiation in a murine tumor model. Murine mammary carcinoma cells, FM3A, were irradiated 7 days after transplantation with a single 5 Gy dose without anesthesia. 31P spectra were measured with a spectrometer up to 30 days. The beta-ATP/Pi and PCr/Pi values were calculated from the peak area of each spectrum. In a fractionation experiment, two fractions of irradiation at a 5 Gy per fraction were given at 0, 1, 2, 3 and 6 day intervals. Tumor growth delay was also scored to determine the fractionated radiation effect. In the control group, beta-ATP/Pi and PCr/Pi decreased with tumor growth. In the single irradiation group, the tumor did not grow up to day 6, and an initial rise and subsequent decrease in beta-ATP/Pi and PCr/Pi were observed. Maximum beta-ATP/Pi and PCr/Pi were observed on day 2 after irradiation. In a fractionation experiment, the greatest growth delay was observed in the two day interval group, in which maximum beta-ATP/Pi and PCr/Pi were demonstrated in 31P-MRS. Our results suggested that changes in the metabolites observed by 31P-MRS could be useful indicators for determining the fractionation schedule in radiation therapy.