Limited data are available on 5FU intratumoral pharmacokinetics. Previous studies with radiolabeled 5FU showed homogeneous uptake in spheroids within a few minutes (Cancer Chemother Pharmacol. 1984;13(2):131-5) but no quantification was done. We present data on intracellular and intra-spheroidal 5FU uptake; drug efflux experiments are on-going and results will be presented.
MCF-7 and HCT-116 cells were used for cellular and spheroid experiments. Spheroid growth was optimized to produce a spheroid of 300-400 µm diameter at day 4. Treatment: 1x106 cells or 30 spheroids/time point were exposed to 10 µM (1300ng/mL) 5FU at
Both MCF-7 and HCT-116 achieved steady state by 20min in cells (1800ng/g aprox.) and 60min in spheroids (330ng/g aprox.) that was maintained at 240min. No 5FUrd was seen but 5FdUrd was identified in the HCT-116 cell line; with 5FdUrd included, total drug levels at steady state were 3000ng/g and 1000ng/g in cells and spheroids, respectively. Although there was variability in the HCT-116 drug levels between experiments, the contour of the drug uptake curve was consistent. MCF-7 spheroids are being analyzed.
5FU uptake ng/g Mean [range]