Tissue penetration and activity of Camptothecins in solid tumor xenografts Kyle et. al. 1 Tissue penetration and activity of Camptothecins in solid tumor xenografts

No conflicts of interest 6 figures Tissue penetration and activity of Camptothecins in solid tumor xenografts Kyle et. al. 2 The ability of a panel of camptothecin derivatives to access the tumor compartment was evaluated to determine the mechanisms by which the architecture of solid tumors may act to limit their activity. Microregional localization and activity of members of the camptothecin class of topoisomerase I targeting agents including topotecan, irinotecan and irinophore C, a lipid-based nanoparticulate formulation of irinotecan, were evaluated over time in HCT116 & HT29 colorectal tumor xenografts. Using native drug fluorescence, their distributions in tissue cryosections were related to the underlying tumor vasculature, tumor cell proliferation and apoptosis. Topotecan exhibited a relatively uniform tumor distribution, in tissue 100-µm away from vessels it reached 94±5 % of levels seen around blood vessels while irinotecan and irinophore C were found to reach only 41±10 % and 5±2% respectively. Surprisingly, all 3 agents were able to initially inhibit proliferation uniformly throughou