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 Ca2+ ion or cell membrane Ca2+ and Na+/Ca2+ ion transport systems are involved in maintaining the cell-associated activity of technetium-99m-hexakis-methoxy-isobutyl-isonitrile (99mTc-MIBI) and technetium-99m-ethylene-bisbis(2-ethoxyethyl)phosphin] (99mTc-tetrofosmin) in tumour cell lines. The cell-associated activities of 99mTc-MIBI and 99mTc-tetrofosmin were assessed in various buffers, with or without Na+ and/or with different concentrations of Ca2+, in Lewi's murine lung cell carcinoma and human glioma cell lines. Different Ca2+ channel modulators, such as verapamil, flunarizine and 3,4-dichlorobenzamil (DCB), were used to assess the effect of Ca2+ channels on the cell-associated activity of 99mTc-MIBI and 99mTc-tetrofosmin. Despite significant differences between cell lines, the cell-associated activity of 99mTc-MIBI was higher in buffers without extracellular Ca2+ and Na+. The cell-associated activity of 99mTc-MIBI was significantly lower in all buffers containing high concentrations of Ca2+ in both cell lines. The cell-associated activity of Tc-tetrofosmin was also significantly higher in buffers without Ca2+, and was significantly decreased in buffers with high concentrations of Ca2+. All modulators significantly increased the cell-associated activity of 99mTc-MIBI in both cell lines in all buffers. All modulators increased the cell-associated activity of 99mTc-tetrofosmin, particularly in buffers containing Ca2+. The cell-associated activities of both 99mTc-MIBI and 99mTc-tetrofosmin may be dependent on verapamil-, flunarizine- and DCB-sensitive Ca2+ channels.