Comparison of the Uptakes of 99mTc-sestamibi and 99mTc-tetrofosmin in Cancer Cell Lines Expressing Multidrug Resistance

Yoo, Jeong Ah; Chung, Shin Young; Seo, Myeng Rang; Kwak, Dong Suk; Ahn, Byeong Cheol; Lee, Kyu Bo; Lee, Jaetae

Abstract

PURPOSE
Cellular uptakes of 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin into cancer cell lines expressing multidrug resistance (MDR) were investigated and compared. The effects of verapamil and cyclosporin A, well-known multidrug resistant reversing agents, on cellular uptakes of both tracers were also compared. MATERIALS AND METHODS: Doxorubicin-resistant HCT15/CL02 human colorectal cell and doxorubicin-resistant K562 (Adr) and vincristine-resistant K562 (Vcr) human leukemic cells were studied. RT-PCR analysis was used for the detection of mdr1 mRNA expression. MDR-reversal effects with verapamil and cyclosporine A were evaluated at different drug concentrations after incubation with MIBI and tetrofosmin for 1, 15, 30, 45 and 60 min, using single-cell suspensions at 1x10 (6) cells/ml incubated at 37 degrees C. Radioactivity in supernatants and pellets were measured with gamma well counter. RESULTS: The cellular uptakes of MIBI and tetrofosmin in K562 (Adr) and K562 (Vcr) were lower than those of parental K562 cell. In HCT15/CL02 cells and K562 (Adr) cells, there were no significant difference in cellular uptakes of both tracers, but cellular uptake of MIBI was higher than that of tetrofosmin in K562 (Vcr) cells. Coincubation with verapamil resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Verapamil increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 11.9- and 6.8-fold, by K562 (Adr) cell by 14.3- and 8-fold and by K562 (Vcr) cell by 7- and 5.7-fold in maximum, respectively. Cyclosporin A increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 10- and 2.4-fold, by K562 (Adr) cell by 44- and 13-fold and by K562 (Vcr) cell by 18.8- and 11.8-fold in maximum, respectively. CONCLUSION: Taking together, MIBI and tetrofosmin are considered as suitable radiopharmaceuticals for detecting multidrug resistance. However, MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators. Since cellular uptakes of both tracers might differ in different cell types, further experiments regarding differences in cellular uptakes between cell types should be explored.