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 perfused tissue-isolated tumors. Human tumor lines MCF-7, U87, and LS174T were implanted in the ovarian fat pad of immune-deficient mice and grown isolated from the surrounding tissue. The initial and continuous tissue uptakes of doxorubicin, daunorubicin, and idarubicin were measured. The clearance of these anthracyclines from the perfused vasculature of the tissue-isolated tumor was calculated using BSA as an intravascular marker. The measured clearances ranged from 50-200 microl/min/g tumor tissue, and the fractional clearances 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 clearances of the anthracyclines or among the tumor lines. The observed similarities in clearance of the anthracyclines was largely explained by differences in their protein binding and tissue diffusion gradients.