Reduction of 99m Tc-sestamibi and 99m Tc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function

Abstract

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of (99m)Tc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, (99m)Tc-tetrofosmin (TF), was also examined. Cellular uptake of (99m)Tc-MIBI and (99m)Tc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N(2) and 5% CO(2) reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.

Clinical Significance of Tetrofosm in Extracardiac Uptake During Myocardial Perfusion Imaging

“…Pathologic uptake of Tc-99m tetrofosmin can occur in benign or malignant tumors and also in infectious or non-infectious diseases (Vijayakumar et al, 2005). The mechanism of uptake of Tc-99m tetrofosmin in non-cardiac lesions is not completely understood, but the size of the lesion, its mitochondrial-rich cellularity and perfusion (factors) play a significant role (Kinuya et al, 2003;Sükan et al, 2004). Over-expression of P-glycoprotein or multi-drug resistance can decrease tumor uptake and are also associated with resistance to cancer treatment.…”

Retention of the Radiotracers 64Cu-ATSM and 64Cu-PTSM in Human and Murine Tumors Is Influenced by MDR1 Protein Expression

“…In general, studies have shown that tumor cells with high MDR1 expression show lower accumulation and faster washout of the tracer than do their parental cells with lower MDR1 expression (5)(6)(7)(8)(9)(10). A few studies have found decreased tumor or tumor cell retention of 99m Tc-MIBI in the presence of lower oxygen tension (7)(8)(9). 99m Tc-MIBI is used for conventional planar imaging or SPECT.…”