Monitoring chemotherapeutic response in RIF-1 tumors by single-quantum and triple-quantum-filtered 23Na MRI, 1H diffusion-weighted MRI and PET imaging

The effects of 5-fluorouracil (5FU, 150 mg/kg, ip) on subcutaneously implanted radiation-induced fibrosarcoma (RIF-1) tumors were monitored by in vivo 1H MRI to evaluate the water apparent diffusion coefficient (ADC), by single-quantum (SQ) and triple-quantum-filtered (TQF) 23Na MRI to evaluate compartmental Na+ content and by positron emission tomography (PET) to evaluate 2-[18F]fluoro-2-deoxy-d-glucose (FDG) uptake in the tumor. The MRI experiments were performed on untreated control and treated mice once before and then daily for 3 days after treatment. The PET experiments were performed on separate groups of age- and tumor-volume-matched animals once before and then 3 days after treatment. Tumor volumes significantly decreased in treated animals 2 and 3 days posttreatment. At the same time points, in vivo MRI measurements showed an increase in both total tissue SQ 23Na signal intensity (SI) and water ADC in treated tumors while control tumors showed no change in these parameters. TQF 23Na SI and FDG uptake were significantly lower in treated tumors compared with control tumors 3 days after 5FU treatment. The correlated increases in total tissue 23Na SI and water ADC following chemotherapy reflect an increase in extracellular space, while the lower TQF 23Na SI and FDG uptake in treated tumors compared with control tumors suggest a shift in tumor metabolism from glycolysis to oxidation and/or a decrease in cell density.