TECHNETIUM-99M-SESTAMIBI UPTAKE BY HUMAN BENIGN AND MALIGNANT BREAST-TUMOR CELLS - CORRELATION WITH MDR GENE-EXPRESSION

Early diagnosis of multidrug-resistance (MDR) development is extremely important for the judicious choice of treatment protocols in breast c ancer chemotherapy. In this study, the mechanism of Tc-99m-sestamibi u ptake by nine human breast tumor cell lines was analyzed as a function of P-glycoprotein (PgP) expression. Methods: Technetium-99m-sestamibi radioactivity incorporation into the cells was determined after diffe rent times of incubation at 37 degrees C. We analyzed the mechanism of Tc-99m-sestamibi uptake as follows: (a) effect of temperature (4 degr ees C); (b) influence of extracellular Tc-99m-sestamibi concentration; and (c) competitive inhibition of cell uptake with cold Tc-99m-sestam ibi. Technetium-(99m)-sestamibi uptake was compared to the level of Pg P determined by Western blotting. The PgP reversing effect of verapami l was evaluated at different drug concentrations (50, 200, 500 mu M). Results: Technetium-(99m)-sestamibi uptake plateaued at 60 min, which was 14 times lower at 4 degrees C than at 37 degrees C and was directl y proportional to the extracellular concentration between 0.3 and 10 n M. Technetium-99m-sestamibi percentage uptake by cells expressing noni mmunodetectable levels of PgP was significantly higher (7.3% +/- 0.6% (s.d.) to 14.9% +/- 1.9%) than that by cells expressing high PgP level s (0.7% +/- 0.4%, p < 0.001). In the presence of verapamil, a known re verser of PgP functions, Tc-99m-sestamibi uptake was increased by a fa ctor of 2 in cells expressing no detectable levels of PgP and by a fac tor of 12 in cells with high PgP levels. Conclusion: Technetium-99m-se stamibi uptake by these breast tumor cells is energy-dependent but not specific. These data suggest that Tc-99m-sestamibi imaging may be use d as a noninvasive technique to diagnose the presence of MDR in breast tumors in vivo.