Effects of extracellular Na+ and Ca2+ ions and Ca2+ channel modulators on the cell-associated activity of 99mTc-MIBI and 99mTc-tetrofosmin in tumour cells

Our aim was to determine whether the Ca ion or cell membrane Ca and Na/Ca ion transport systems are involved in maintaining the cell-associated activity of technetium-99m-hexakis-methoxy-isobutyl-isonitrile (Tc-MIBI) and technetium-99m-ethylene-bis[bis(2-ethoxyethyl)phosphin] (Tc-tetrofosmin) in tumour cell lines. The cell-associated activities of Tc-MIBI and Tc-tetrofosmin were assessed in various buffers, with or without Na and/or with different concentrations of Ca, in Lewiʼs murine lung cell carcinoma and human glioma cell lines. Different Ca channel modulators, such as verapamil, flunarizine and 3,4-dichlorobenzamil (DCB), were used to assess the effect of Ca channels on the cell-associated activity of Tc-MIBI and Tc-tetrofosmin. Despite significant differences between cell lines, the cell-associated activity of Tc-MIBI was higher in buffers without extracellular Ca and Na. The cell-associated activity of Tc-MIBI was significantly lower in all buffers containing high concentrations of Ca in both cell lines. The cell-associated activity of Tc-tetrofosmin was also significantly higher in buffers without Ca, and was significantly decreased in buffers with high concentrations of Ca. All modulators significantly increased the cell-associated activity of Tc-MIBI in both cell lines in all buffers. All modulators increased the cell-associated activity of Tc-tetrofosmin, particularly in buffers containing Ca. The cell-associated activities of both Tc-MIBI and Tc-tetrofosmin may be dependent on verapamil-, flunarizine- and DCB-sensitive Ca channels.