Cellular membrane permeability of anthracyclines does not correlate with their delivery in a tissue-isolated tumor

The clearance of anthracyclines from the vasculature was studied in perfuse d tissue-isolated tumors. Human tumor lines MCF-7, U87, and LS174T were imp lanted in the ovarian fat pad of immune-deficient mice and grown isolated f rom the surrounding tissue. The initial and continuous tissue uptakes of do xorubicin, daunorubicin, and idarubicin were measured. The clearance of the se anthracyclines from the perfused vasculature of the tissue-isolated tumo r was calculated using BSA as an intravascular marker. The measured clearan ces ranged from 50-200 mu l/min/g tumor tissue, and the fractional clearanc es were between 0.30 and 0.70. On the basis of the in vitro cellular uptake rates of the anthracyclines, we expected a higher clearance of idarubicin than of doxorubicin. No significant differences were found among the cleara nces of the anthracyclines or among the tumor lines. The observed similarit ies in clearance of the anthracyclines was largely explained by differences in their protein binding and tissue diffusion gradients.