DETECTION OF TUMOR RESPONSE TO CHEMOTHERAPY BY H-1 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY - EFFECT OF 5-FLUOROURACIL ON LACTATE LEVELS IN RADIATION-INDUCED FIBROSARCOMA-1 TUMORS

The aim of this study was to evaluate the ability of noninvasive H-1 m agnetic resonance spectroscopic imaging to detect the response of radi ation-induced fibrosarcoma 1 tumors to treatment with 5-fluorouracil ( 5-FU). Parallel magnetic resonance studies of tumor extracts and assay s of apoptosis and necrosis in tumor sections were performed to elucid ate 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, an d tumor shrinkage within 48 h. No significant change in normalized tri methylamine and lactate levels was observed during 3 days of untreated tumor growth. Following treatment with 5-FU, normalized intensities o f both trimethylamine and lactate decreased significantly from pretrea tment levels within 24 h and continued to decline at 48 h, The decreas e in lactate levels determined by spectroscopic imaging in vivo was al so observed in perchloric acid extracts of radiation-induced fibrosarc oma 1 tumors, Possible mechanisms for the decrease of tumor lactate le vels include increased blood flow and decreased glycolytic rate, Unlik e lactate, changes in normalized trimethylamine levels observed in viv o were not observed in tumor extracts, The mechanism underlying the an omalous decrease in the in vivo trimethylamine level is under investig ation, These findings demonstrate that lactate is a reliable and sensi tive indirect indicator of response to 5-FU in at least one tumor mode l and point to the possible clinical utility of this resonance as an i ndex of clinical tumor response to chemotherapy.