The aim of this study was to evaluate the ability of noninvasive 1H magnetic resonance spectroscopic imaging to detect the response of radiation-induced fibrosarcoma 1 tumors to treatment with 5-fluorouracil (5-FU). Parallel magnetic resonance studies of tumor extracts and assays of apoptosis and necrosis in tumor sections were performed to elucidate the mechanism underlying the changes detected in spectra in vivo. Cell death in tumors after a single dose of 5-FU (165 mg/kg, i.p.) was characterized by increased apoptosis, decreased necrotic fraction, and tumor shrinkage within 48 h. No significant change in normalized trimethylamine and lactate levels was observed during 3 days of untreated tumor growth. Following treatment with 5-FU, normalized intensities of both trimethylamine and lactate decreased significantly from pretreatment levels within 24 h and continued to decline at 48 h. The decrease in lactate levels determined by spectroscopic imaging in vivo was also observed in perchloric acid extracts of radiation-induced fibrosarcoma 1 tumors. Possible mechanisms for the decrease of tumor lactate levels include increased blood flow and decreased glycolytic rate. Unlike lactate, changes in normalized trimethylamine levels observed in vivo were not observed in tumor extracts. The mechanism underlying the anomalous decrease in the in vivo trimethylamine level is under investigation. These findings demonstrate that lactate is a reliable and sensitive indirect indicator of response to 5-FU in at least one tumor model and point to the possible clinical utility of this resonance as an index of clinical tumor response to chemotherapy.
This work was supported by NIH Grant 1RO1 CA51930.