Tumor Bioenergetics and Blood Flow in RIF-1 Murine Tumors Treated with 5-fluorouracil

Treatment of RIF-1 solid tumors with 5-fluorouracil (5-FU, 100 or 200 mg/kg, ip) caused substantial regression of the tumors, with regrowth initiated on Day 6 (100 mg/kg) or Day 9 (200 mg/kg). Blood perfusion in the tumor, estimated by uptake of 86Rb+, was significantly increased after treatment with 5-FU, while Rb+ uptake in normal tissues (skin, muscle) was unaffected. The increase in tumor perfusion during the first few days following treatment was significantly greater in animals treated with the higher dose of 5-FU. Perfusion-dependent 86Rb+ uptake returned to control levels by the 9th day after treatment with 100 mg/kg of 5-FU, but remained elevated on Days 9-12 after the higher dose. By the 1st day following treatment with 5-FU, in vivo 31P NMR spectra of treated tumors indicated significantly higher ratios of phosphocreatine to Pi, higher pH, and lower ratios of Pi to nucleoside triphosphates compared to untreated age-matched controls. These changes persisted for 9 days following the lower 5-FU dose and for at least 12 days following the higher dose. Treatment with 5-FU induces profound, dose-dependent changes in tumor bioenergetics, which may result, at least in part, from changes in tumor perfusion after cytoreduction.