31P magnetic resonance spectroscopy detection of response-predictive adenosine triphosphate decrease in irradiated radiation-induced fibrosarcoma-1 tumors.

Abstract

In previous phosphorus-31 (31P) magnetic resonance (MR) spectroscopy studies of radiation-induced fibrosarcoma (RIF-1), tumor model single-dose x-ray irradiation was applied at subcurative doses. A more effective x-ray does was used in this study, allowing correlation of treatment efficacy with the early changes observed in the 31P MR spectra of RIF-1 tumors. Subcutaneous RIF-1 tumors of 60 mice were examined by 31P MR spectroscopy shortly before a single localized x-ray dose of 40 Gy and at eight times (2, 12, 24, 48, 72, 120, 168, and 216 hours) thereafter. Early increases in the relative concentration of inorganic phosphate and decreases in adenosine triphosphate (ATP), most notably at 2 and 12 hours (each P < 0.00001), were observed that lasted up to 48 hours after irradiation. Phosphomonoester and tumor pH showed decreases that reversed even earlier. Reduction of ATP measured at 48 hours after irradiation was, however, correlated with percent tumor shrinkage observed during the subsequent weeks (r = -0.59; P < 0.00001). Sustained loss of RIF-1 tumor ATP is predictive of treatment efficacy. Temporary depression of high-energy phosphate in favor of inorganic phosphate does not necessarily lead to cell death.