MRP-1 Protein Expression and Glutathione Content of In Vitro Tumor Cell Lines Derived from Human Glioma Carcinoma U-87-MG Do Not Interact with 99 mTc-Glucarate Uptake

Abstract

The main cause of the multidrug resistance (MDR) of glioma cells is the overexpression of MRP-1, often associated with high levels of glutathione (GSH). We investigated whether MRP-1-related GSH content can influence ^99mTc-glucarate entry by comparing its uptake with that of ^99mTc-sestamibi (MIBI), an MRP- 1 probe, in an in vitro model of a sensitive cell line (U-87-MG) and a resistant derived cell line expressing MRP-1 (U-87-MG-R). Drug resistance was assessed by immunoblotting, GSH measurement, and Alamar Blue™ assay. To correlate MDR phenotype with tracer accumulation, uptakes were performed with and without modulators and after GSH depletion. Similar accumulation of ^99mTc-glucarate was observed in the two cell lines, and the use of MDR reversals did not enhance its uptake. Our results clearly demonstrate that ^99mTc-glucarate uptake is not related to MRP-1 expression or GSH levels. In contrast, ^99mTc- MIBI accumulation is inversely proportional to the cell MDR phenotype. The combination of ^99mTc-glucarate and ^99mTc-MIBI may be a useful tool for the noninvasive detection of malignant sites and their chemoresistance status.