^99mTc-sestamibi is a substrate for P-glycoprotein and the multidrug resistance-associated protein

^99mTc-sestamibi (^99mTc-MIBI) is a substrate for the P-glycoprotein (P-gp) pump but it is not known whether it is a substrate for the multidrug resistance-associated protein (MRP) pump. Therefore, ^99mTc-MIBI was evaluated in the GLC₄ cell line and its doxorubicin-resistant MRP-, but not P-gp-, overexpressing GLC₄/ADR sublines as well as in the S1 cell line and its MRP-transfected subline S1-MRP. ^99mTC-MIBI concentration decreased in the GLC₄/ADR sublines with increasing MRP overexpression and was lower in S1-MRP than in S1. ^99mTC-MIBI plus vincristine increased ^99mTc-MIBI concentration in GLC₄ lines compared with ^99mTc-MIBI alone. ^99mTc-MIBI efflux raised with increasing MRP expression in the GLC₄ lines. Glutathione depletion elevated ^99mTC-MIBI concentration in GLC₄/ADR(150x). Cross resistance for ⁹⁹Tc-MIBI, used to test cytotoxicity of the Tc compound, was observed in GLC₄/ADR(150x) vs GLC₄. ⁹⁹Tc-MIBI induced a synergistic effect on vincristine cytotoxicity in GLC₄/ADR(150x). These results show that ^99mTc-MIBI is involved in MRP-mediated efflux. The fact that ^99mTc-MIBI efflux is influenced by MDR1 and MRP expression must be taken into account when this γ-rays-emitting complex is tested for tumour efflux measurements.