P-31 MAGNETIC-RESONANCE SPECTROSCOPY DETECTION OF RESPONSE-PREDICTIVEADENOSINE-TRIPHOSPHATE DECREASE IN IRRADIATED RADIATION-INDUCED FIBROSARCOMA-1 TUMORS

RATIONALE AND OBJECTIVES. In previous phosphorus-31 (P-31) magnetic re sonance (MR) spectroscopy studies of radiation-induced fibrosarcoma (R IF-1), tumor model single-dose x-ray irradiation was applied at subcur ative doses. A more effective x-ray dose was used in this study, allow ing correlation of treatment efficacy with the early changes observed in the P-31 MR spectra of RIF-1 tumors. METHODS. Subcutaneous RIF-1 tu mors of 60 mice were examined by P-31 MR spectroscopy shortly before a single localized x-ray dose of 40 Gy and at eight times (2, 12, 24, 4 8, 72, 120, 168, and 216 hours) thereafter. RESULTS. Early increases i n the relative concentration of inorganic phosphate and decreases in a denosine 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 earl ier. Reduction of ATP measured at 48 hours after irradiation was, howe ver, correlated with percent tumor shrinkage observed during the subse quent weeks (r = -0.59; P < 0.00001). CONCLUSIONS. Sustained loss of R IF-1 tumor ATP is predictive of treatment efficacy. Temporary depressi on of high-energy phosphate in favor of inorganic phosphate does not n ecessarily lead to cell death.