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Comparative ^99mTc-Sestamibi and ³H-Daunomycin Uptake in Human Carcinoma Cells: Relation to the MDR Phenotype and Effects of Reversing Agents

Transfert Laboratory and Division of Nuclear Medicine, Centre Jean Perrin, and INSERM U484, Clermont-Ferrand, France

Correspondence: For correspondence or reprints contact: Anne Cayre, Eng, Transfert Laboratory, Centre Jean Perrin, BP 392, 63011 Clermont-Ferrand Cédex 1, France.

ABSTRACT

Because ^99mTc-sestamibi (MIBI) appears to be a potent candidate for multidrug resistance (MDR) evaluation in tumors, its cellular uptake should be similar to that of ³H-daunomycin in a variety of conditions of expression and inhibition of MDR activity. Methods: We used a human rhinopharyngeal carcinoma cell line (KB-3–1) and its MDR variant (KB-A1). Cells were incubated 2 h with ^99mTc-MIBI and ³H-daunomycin under control conditions or in the presence of a reversing agent such as verapamil (10 µmoI/L), PSC833 (1 µmoI/L) or S9788 (5 µmoI/L). Results: Relative to the KB-3–-1-sensitive cells, accumulations of ^99mTc-MIBI and ³H-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 99mTc-MIBI (138% ± 25%; P < 0.01), whereas the intracellular uptake of ³H-daunomycin was markedly increased with the three reversing agents (up to 311% ± 37% with S9788; P < 0.001). With this last treatment, uptake of ³H-daunomycin in KB-A1 cells nearly returned to its basal level in sensitive cells. Conclusion: ^99mTc-MIBI monitors the MDR phenotype of tumor cells effectively but responds to reversing agents differently than ³H-daunomycin.

Key Words: multidrug resistance phenotype • ^99mTc-sestamibi • ³H-daunomycin • multidrug resistance reversing agents