Ion transport systems in the uptake of Tc-99(m)-tetrofosmin, Tc-99(m)-MIBI and Tl-201 in a tumour cell line

The kinetics, intracellular distribution and effects of ion transport inhibitors on the uptake of Tc-99(m) tetrofosmin, Tc-99(m)-methoxyisobutyl isonitrile (Tc-99(m)-MIBI) and Tl-201 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 m-chlorophenylhydrazone (CCCP) was used to study the release of the tracers. The tracers showed similar uptake and washout kinetics. Ouabain inhibited 55-67% of Tl-201, 16-22% of T-99(m)-tetrofosmin and 8-14% of Tc-99(m)-MIBI. DMA inhibited the uptake of both Tc-99(m)-tetrofosmin (30%) and Tc-99(m)-MIBI(21%). Bumetanide stimulated the uptake of Tc-99(m)-tetrofosmin and Tc-99(m)-MIBI but inhibited that of Tl-201 (37%). When cells were pretreated with various combinations of these ion transport inhibitors, the uptake of Tl-201 was related to Na+, K+ pump, Na+,K+,2Cl(-) co-transport systems, whereas the uptake of both Tc-99(m)-tetrofosmin and Tc-99(m)-MIBI was related to the Na+,K+ pump, Na+/H+ antiport systems. Addition of CCCP released 55% and 90% of accumulated Tc-99(m)-tetrofosmin and Tc-99(m)-MIBI respectively, indicating that the percentage released was related to mitochondrial uptake.