Ion transport systems in the uptake of ⁹⁹tc^m-tetrofosmin, ⁹⁹tc^m-mibi and ²⁰¹t1 in a tumour cell line

The kinetics, intracellular distribution and effects of ion transport inhibitors on the uptake of ⁹⁹Tc^m-tetrofosmin, ⁹⁹Tc^m-methoxyisobutyl isonitrile (⁹⁹Tc^m-MIBI) and ²⁰¹TI were investigated in a tumour cell line. Both uptake and washout of the tracers were measured at specific intervals. Cells were treated with ouabain, dimethyl amiloride (DMA) and bumetanide to observe the effects on uptake, while carbonyl cyanide w-chlorophenylhydrazone (CCCP) was used to study the release of the tracers. The tracers showed similar uptake and washout kinetics. Ouabain inhibited 55-67% of ²⁰¹TI, 16-22% of ⁹⁹Tc^m-tetrofosmin and 8-14% of ⁹⁹Tc^m-MIBI. DMA inhibited the uptake of both ⁹⁹Tc^m-tetrofosmin (30%) and ⁹⁹Tc^m-MIBI (21%). Bumetanide stimulated the uptake of ⁹⁹Tc^m-tetrofosmin and ⁹⁹Tc^m-MIBI but inhibited that of ²⁰¹TI (37%). When cells were pretreated with various combinations of these ion transport inhibitors, the uptake of ²⁰¹TI was related to Na⁺, K⁺ pump, Na⁺, K⁺,2Cl⁻ co-transport systems, whereas the uptake of both ⁹⁹Tc^m-tetrofosmin and ⁹⁹Tc^m-MIBI was related to the Na⁺, K⁺ pump, Na⁺/H⁺ antiport systems. Addition of CCCP released 55% and 90% of accumulated ⁹⁹Tc^m-tetrofosmin and ⁹⁹Tc^m-MIBI respectively, indicating that the percentage released was related to mitochondrial uptake.