Comparison of Tc-99m-sestamibi and doxorubicin to monitor inhibition of P-glycoprotein function

P-glycoprotein (Pgp) overexpression is a well-recognized factor in resistan ce to chemotherapy, Doxorubicin flow cytometry is used to monitor Pgp funct ion in haematological specimens and biopsies from other cancers, and radion uclide imaging with sestamibi has recently shown promise for non-invasive m onitoring. In the present study the two methods were directly compared in s ingle-cell suspensions of three variants of the hu man breast carcino ma ce ll line MCF7: sensitive MCF7/WT, doxorubicin-selected MGF7/AdrR, and MDR1-g ene-transfected MCF7/BC19 cells with doxorubicin resistance factors of 1, 1 92, and 14, respectively. Accumulation of sestamibi and mean fluorescence o f doxorubicin (5.5 muM) were assessed over 60 min in the presence and absen ce of Pgp modulators GG918 (0.01 to 0.2 muM) and PSC833 (0.05 to 2.0 muM). Accumulation curves for sestamibi and doxorubicin differed among the cell V ariants under control conditions, with sestamibi showing a significantly gr eater difference between WT and resistant cells than doxorubicin. Both GG91 8 and PSC833 reversed uptake deficits to WT levels for sestamibi in MCF7/BC 19 cells and doxorubicin in MCF7/BG19 and MCF7/AdrR cells, but failed to sh ow the same effect for sestamibi in MCF7/AdrR cells (similar to 30% of MCF7 /WT level). Thus, both methods clearly distinguished sensitive from resista nt MCF7 variants, with the radionuclide method showing greater sensitivity. (C) 2001 Cancer Research Campaign.