The Multidrug Resistance of In Vitro Tumor Cell Lines Derived from Human Breast Carcinoma MCF-7 Does Not Influence Pentavalent Technetium-99m-Dimercaptosuccinic Acid Uptake

Abstract

The main causes of multidrug resistance (MDR) are overexpression of P-glycoprotein (P-gp) and multidrug resistance-associated protein isoform 1 (MRP1) often associated with high levels of glutathione (GSH). We investigated whether MDR phenotype can influence Tc-99m-(V)-DMSA [pentavalent technetium-99m-dimercaptosuccinic acid] entry by comparing its uptake with that of Tc-99m-sestamibi (MIBI) on an in vitro model of sensitive (MCF-7) and variant resistant cell lines. Drug resistance was assessed by immunoblotting, GSH measurement, and 3-[4,5-dimethylthiazol-2-yl]-2,5,diphenyl tetrazolium bromide (MTT) assay. To correlate MDR phenotype with tracer accumulation, uptakes were performed with and without P-gp and MRP1 inhibitors and after GSH modulation. Similar accumulation of Tc-99m-(V)-DMSA was observed in all cell lines and the use of MDR reversals did not enhance its uptake. Our results demonstrate clearly that Tc-99m-(V)-DMSA uptake is not related to either P-gp and MRP1 expression, or GSH levels. In contrast, Tc-99m-MIBI accumulation is inversely proportional to the cell MDR phenotype. The combination of Tc-99m-(V)-DMSA and Tc-99m-MIBI may be a useful tool for noninvasive detection of malignant sites and their chemoresistance status.