Comparative Tc-99m-sestamibi and H-3-daunomycin uptake in human carcinoma cells: Relation to the MDR phenotype and effects of reversing agents

Because Tc-99m-sestamibi (MIBI) appears to be a potent candidate for multid rug resistance (MDR) evaluation in tumors, its cellular uptake should be si milar to that of H-3-daunomycin in a variety of conditions of expression an d inhibition of MDR activity. Methods: We used a human rhinopharyngeal carc inoma cell line (KB-3-1) and its MDR variant (KB-A1). Cells were incubated 2 h with (TC)-T-99m-MIBI and H-3-daunomycin under control conditions or in the presence of a reversing agent such as verapamil (10 mu mol/L), PSC833 ( 1 mu mol/L) or S9788 (5 mu mol/L). Results: Relative to the KB-3-1-sensitiv e cells, accumulations of Tc-99m-MIBI and H-3-daunomycin were reduced to 31 % +/- 5% and 36% +/- 11% (P < 0.001 for both) in KB-A1-resistant cells. In sensitive cells, accumulation of both agents was increased by verapamil and PSC833 (range 115%-140%; P < 0.05) but not by S9788. In KB-A1 cells, only S9788 significantly increased the cellular uptake of Tc-99m-MIBI (138% +/- 25%; P < 0.01), whereas the intracellular uptake of H-3-daunomycin was mark edly increased with the three reversing agents (up to 311% +/- 37% with S97 88; P < 0.001). With this last treatment, uptake of H-3-daunomycin in KB-A1 cells nearly returned to its basal level in sensitive cells. Conclusion: T c-99m-MIBI monitors the MDR phenotype of tumor cells effectively but respon ds to reversing agents differently than H-3-daunomycin.