Technetium-99m-sestamibi uptake by human benign and malignant breast tumor cells: correlation with mdr gene expression.

UNLABELLED

Early diagnosis of multidrug-resistance (MDR) development is extremely important for the judicious choice of treatment protocols in breast cancer chemotherapy. In this study, the mechanism of 99mTc-sestamibi uptake 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 different times of incubation at 37 degrees C. We analyzed the mechanism of 99mTc-sestamibi uptake as follows: (a) effect of temperature (4 degrees C); (b) influence of extracellular 99mTc-sestamibi concentration; and (c) competitive inhibition of cell uptake with cold 99mTc-sestamibi. Technetium-99m-sestamibi uptake was compared to the level of PgP determined by Western blotting. The PgP reversing effect of verapamil was evaluated at different drug concentrations (50, 200, 500 microM).

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 directly proportional to the extracellular concentration between 0.3 and 10 nM. Technetium-99m-sestamibi percentage uptake by cells expressing nonimmunodetectable levels of PgP was significantly higher (7.3% +/- 0.6% (s.d.) to 14.9% +/- 1.9%) than that by cells expressing high PgP levels (0.7% +/- 0.4%, p < 0.001). In the presence of verapamil, a known reverser of PgP functions, 99mTc-sestamibi uptake was increased by a factor of 2 in cells expressing no detectable levels of PgP and by a factor of 12 in cells with high PgP levels.

CONCLUSION

Technetium-99m-sestamibi uptake by these breast tumor cells is energy-dependent but not specific. These data suggest that 99mTc-sestamibi imaging may be used as a noninvasive technique to diagnose the presence of MDR in breast tumors in vivo.