Cytotoxic drug penetration studies in multicellular tumour spheroids.

1. The three-dimensional structure of human lung tumour spheroids conferred a degree of resistance to the anthracyclines adriamycin, 4'-deoxydoxorubicin, daunomycin and daunomycin-low density lipoprotein complex in comparison with cells grown as a monolayer, as assessed by delayed growth and clonogenic cell survival. 2. 4'-Deoxydoxorubicin induced a longer growth delay and greater clonogenic cell kill than adriamycin in spheroids, although it was no more cytotoxic in monolayer. 3. Fluorescent microscopy demonstrated that the more lipophilic analogues partitioned into the spheroid more rapidly and to a greater degree than adriamycin. 4. The spheroid model demonstrated that penetration is an important aspect of resistance to anthracycline drugs, and this approach may represent a better in vitro system for testing lipophilic analogues of cytotoxic drugs.