AIM:: To study the accumulation and washout kinetics of [^99mTc]-hexakis-2-methoxyisobutyl isonitrile (^99mTc-MIBI) in MDR positive and MDR negative tumour cells and how this is modified by lipophilic P-glycoprotein ligands.

The tumour cells were incubated in the presence and absence of the ligands and the uptakes of ^99mTc-MIBI, rhodamine 123 and 2-[¹⁸F]fluoro-2-deoxy-d-glucose (¹⁸FDG) were measured.

The accumulation of ^99mTc-MIBI in the tumour cells followed biphasic kinetics. Verapamil and cyclosporin A increased the membrane fluidity and significantly enhanced the ^99mTc-MIBI uptake of the MDR negative cells, while the rhodamine 123 uptake was not affected. Verapamil significantly increased the uptake of rhodamine 123 and ¹⁸FDG but did not modify that of ^99mTc-MIBI in the MDR positive cells. Cyclosporin A significantly increased the ¹⁸FDG uptake of the MDR positive and negative tumour cells; these effects were ouabain-sensitive. Depolarization of the cytoplasmic membrane, acidification of the extracellular medium and the administration of CCCP decreased the accumulation of ^99mTc-MIBI and rhodamine 123 uptake in the tumour cells.

Lipophilic P-glycoprotein ligands modified the biphasic accumulation kinetics of the ^99mTc-MIBI uptakes of MDR negative and positive tumour cells in different and complex ways and could therefore mask the P-glycoprotein pump-dependent changes in tracer accumulation.