Tc-99m-Mibi Uptake As A Marker Of Mitochondrial Membrane Potential In Cancer Cells And Effects Of Mdr1 And Verapamil

We investigated the relation of Tc-99m-MIBI uptake to mitochondrial membrane potential (MMP) in cancer cell lines and patient-derived tumor cells (PDCs). In T47D and HT29 cells with low MDR1 expression, FCCP dose-dependently reduced MMP and Tc-99m-MIBI accumulation in similar patterns with nearly perfect linear relationships. T47D and HT29 cells with high MDR1 expression had low Tc-99m-MIBI accumulation that was minimally affected by FCCP dose. In these cells, verapamil markedly increased Tc-99m-MIBI accumulation to magnitudes that were excessive compared to MMP increase. Decreased plasma membrane potential by verapamil and its recovery by FCCP suggested that enhanced Tc-99m-MIBI transport through modified plasma membranes contributed to the excess accumulation. Evaluation of three different colon cancer PDCs with low to modest MDR1 expression verified that FCCP significantly suppressed MMP and similarly reduced Tc-99m-MIBI accumulation. Verapamil partially recovered both MMP and Tc-99m-MIBI accumulation that was lowered by FCCP. Importantly, a high linear correlation was found (r = 0.865) between Tc-99m-MIBI accumulation and MMP in these cells. These findings indicate that low baseline Tc-99m-MIBI uptake that is markedly increased by verapamil represents cancer cells with high levels of MDR1 expression. However, in cancer cells with low or modest levels of MDR1 expression that do not markedly increase Tc-99m-MIBI uptake by verapamil, the magnitude of uptake is largely dependent on cellular MMP.