Uptake of technetium-99m-tetrofosmin, technetium-99m-MIBI and thallium- 201 in tumor cell lines

We investigated the kinetics, cellular uptake and intracellular distribution of ^99mTc-tetrofosmin in tumor cell lines and compared them with those of ^99mTc-MIBI and ²⁰¹Tl. Methods: At specific intervals after incubation with radiotracers, cellular uptake was determined. Cells were also treated with nigericin, carbonyl cyanide m-chlorophenylhydrazone (CCCP) and ouabain to determine their effects on the uptake of the tracers. Results: Each tracer showed similar uptake kinetics in both cell lines, and a steady-state was maintained for at least 4 hr. Nigericin stimulated the uptake of both ^99mTc-tetrofosmin and ^99mTc-MIBI in HBL-2 cells, although it inhibited their uptake in SW-13 cells. Nigericin also inhibited 90% of ²⁰¹Tl uptake in both cell lines. Addition of CCCP caused 73%-97% release of accumulated ^99mTc-MIBI from both cell lines with or without nigericin pretreatment, indicating that most of the accumulated ^99mTc- MIBI was related to mitochondria. The effect of CCCP on accumulated ^99mTc- tatrofosmin was less marked than that on ^99mTc-MIBI in both cell lines, indicating that only a part of accumulated ^99mTc-tetrofosmin, was related to mitochondria. Ouabain preincubation inhibited 74%-77% and 51%-53% of ²⁰¹Tl uptake in HBL-2 and SW-13 cells, respectively, as well as inhibited 22%-31% uptake of ^99mTc-tetrofosmin in both HBL-2 and SW-13 cells. Uptake by the dead ceils of either cell line was negligible for each tracer. Conclusion: Technetium-99m-tetrofosmin uptake depends on both cell membrane and mitochondrial potentials. Only a small fraction of ^99mTc-tetrofosmin accumulates inside the mitochondria, while most ^99mTc-MIBI accumulates inside the mitochondria. Thallium-201 uptake is partly independent of the Na⁺, K⁺ pump.