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.