Technetium-99m-tetrofosmin, Technetium-99m-MIBI and Thallium-201 uptake in rat myocardial cells

The mechanisms of uptake and intracellular distribution of ^99mTc- tetrofosmin, ^99mTc-MIBI and ²⁰¹TI and the behaviors of ^99mTc- tetrofosmin and ^99mTc-MIBI in relation to Na⁺ were studied with primary cultures of myocardial cells. Methods: Both the uptake and the washout of the tracers were sequentially measured. The cells were treated with ouabain, bumetanide, tetrodotoxin, dimethyl amiloride (DMA), nigericin and carbonyl cyanide m-chlorophenylhydrazone (CCCP) to observe the effects of the uptake and intracellular distribution of the traders. Cells equilibrated in buffers with or without Na⁺ were treated with monensin and DMA to evaluate the effect of Na⁺ on the accumulation of the tracers. Results: Despite the similarities in uptake kinetics, there was a higher level of retention of ^99mTc-tetrofosmin inside the cells. Ouabain, bumetanide and tetrodotoxin did not show any inhibitory effect on the uptake of ^99mTc-tetrofosmin and ^99mTc-MIBI, whereas they produced various degrees of inhibition of ²⁰¹TI uptake. DMA produced approximately 35% inhibition of ^99mTc- tetrofosmin uptake and 50% inhibition of ^99mTc-MIBI uptake. Nigericin increased the uptake of ^99mTc-MIBI by the cells. The addition of CCCP produced the release of 38% of the accumulated ^99mTc-tetrofosmin and 52%- 70% of the accumulated ^99mTc-MIBI, indicating that these percentages of accumulation were related to mitochondrial uptake. Neither Na⁺ -free buffer nor monensin had any significant effect on ^99mTc-tetrofosmin accumulation, but they both caused increased accumulation of ^99mTc-MIBI. Conclusion: The uptake of both ^99mTc-tetrofosmin and ^99mTc-MIBI through the cell membrane is partly related to the Na⁺/H⁺ antiporter system. Only part of the accumulated ^99mTc-tetrofosmin inside the cells enters into mitochondria; most of the accumulated ^99mTc-MIBI is related to mitochondrial uptake. This uptake may be related to Na⁺.