In vitro comparison of sestamibi, tetrofosmin, and furifosmin as agents for functional imaging of multidrug resistance in tumors

Sestamibi, tetrofosmin, and furifosmin are Tc-99m-labeled myocardial perfus ion imaging agents which have been shown to be substrates for P-glycoprotei n (Pgp), the multidrug-resistance transporter which is overexpressed in som e tumors. The three tracers were directly compared in vitro in the human br east cancer cell line MCF7-WT and two multidrug-resistant variants, MCF7-BC 19 (MDR1 gene transfected) and MCF7-AdrR (doxorubicin selected). Tracer acc umulation over the course of 60 minutes was determined Dose-response curves were generated for two modulators of Pgp function, GG918 and PSC833. The g eneral shape of accumulation curves for the three tracers in MCF7-WT cells was similar, with accumulation levels being sestamibi > tetrofosmin >furifo smin. Accumulation of sestamibi and furifosmin in MCF7-BC19 cells was reduc ed to 10% and 21% of MCF7-WT levels, respectively, but this accumulation de ficit could be completely reversed by addition of 0.1 mu M GG918 or 2 mu MP SC833. Accumulation of sestamibi and tetrofosmin in MCF7-AdrR cells was 1.6 % and 12% of MCF7-WT levels, respectively. and could only be enhanced to 30 % and 45% of MCFT-WT levels by addition of GG918 or PSC833. In contrast fur ifosmin showed similar levels of accumulation in MCF7-WT and MCF7-BC19 cell s, slightly lower levels in MCF7-AdrR cells, and no consistent response to Pgp modulators. These results support the continued investigation of sestam ibi and tetrofosmin as agents for functional imaging of multidrug resistanc e in human cancer.