Effects of ion channel modulators in the influx and efflux of Tc-99m- MIBI

Possible involvement of cell membrane ion transport systems in the uptake and extrusion of Tc-99m-MIBI was investigated by using various buffers with or without Na⁺ and Ca⁺⁺, and ion transport inhibitors in a tumor cell line. The ion transport modulators dimethyl amiloride (DMA), verapamil, flunarizine and monensin were used. The uptake of Tc-99m-MIBI was significantly increased in all buffers containing either Na⁺ or Ca⁺⁺ alone or none of them. There was significantly increased uptake of Tc-99m-MIBI especially in buffers without Na⁺. Verapamil, a L-type Ca⁺⁺ channel blocker, increased Tc-99m-MIBI uptake in all buffers. Flunarizine, which inhibits Na⁺/Ca⁺⁺ channels, caused significantly increased accumulation of Tc-99m-MIBI only in buffer containing both Na⁺ and Ca⁺⁺. Monensin, a sodium ionophore, significantly increased uptake of Tc-99m-MIBI. DMA, a potent Na⁺/H⁺ antiport inhibitor, significantly inhibited the uptake of Tc- 99m-MIBI in all buffers. In conclusion, Tc-99m-MIBI behaves like Na⁺ during its uptake and extrusion. Extrusion of Tc-99m-MIBI may involve both verapamil- and flunarizine-sensitive pathways.