Comparative 99mTc-sestamibi and 3H-daunomycin uptake in human carcinoma cells: relation to the MDR phenotype and effects of reversing agents.
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 pmol/L), PSC833 (1 micromol/L) or S9788 (5 micromol/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.


CONCLUSIONS
99mTc-MIBI monitors the MDR phenotype of tumor cells effectively but responds to reversing agents differently than 3H-daunomycin.
Cayre
A
A
Transfert Laboratory and Division of Nuclear Medicine, Centre Jean Perrin, and INSERM U484, Clermont-Ferrand, France.
Moins
N
N
Finat-Duclos
F
F
Maublant
J
J
Verrelle
P
P
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D003630:Daunorubicin / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple; D006801:Humans; D010880:Piperidines / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics*; D014227:Triazines / Q000494:pharmacology; D014316:Tritium; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D003524:Cyclosporins; D010880:Piperidines; D019275:Radiopharmaceuticals; D014227:Triazines; D014316:Tritium; C077022:S 9788; D017256:Technetium Tc 99m Sestamibi; D014700:Verapamil; C070272:valspodar; D003630:Daunorubicin