Comparison of the accumulation and efflux kinetics of technetium-99m sestamibi and technetium-99m tetrofosmin in an MRP-expressing tumour cell line

The potential clinical use of technetium-99Pn labeled sestamibi (Tc-MIBI) a nd tetrofosmin (Tc-Tfos) to image tumours is currently being evaluated. In this study, the accumulation and efflux of Tc-MIBI and Tc-Tfos in the nasop haryngeal carcinoma cell line CNE-I were examined in the presence or absenc e of various inhibitors of P-glycoprotein (PGP) and/or multidrug resistance associated protein (MRP) activity [GG918, PSC833, verapamil (Vrp), cyclosp orin A (CsA) and buthionine sulfoximine (BSO)]. Reverse-transcriptase polym erase chain reaction analysis and immunodetection of the CNE-1 cells detect ed expression of MRP, MRP1 and MRP2 but not PGP. Tc-MIBI and Tc-Tfos accumu lation was increased (P < 0.0001) and efflux decreased (P < 0.05) in the pr esence of BSO, CsA, Vrp and PSC833 but not GG918, which is a specific inhib itor of PGP. The absolute accumulation of Tc-MIBI was approximately twofold higher than that seen with Tc-Tfos, whereas the addition of inhibitors cau sed a much greater suppression of Tc-Tfos transport (>2 times greater than for Tc-MIBl). However, no qualitative differences in inhibitors were seen b etween Tc-MIBI and Tc-Tfos. These results suggest that both Tc-MIBI and Tc- Tfos are substrates for the MRP transporter and that PSC833, Vrp, CsA and B SO but not GG918 can inhibit MRP activity. These results indicate that Tc-M IBI and Tc-Tfos may be suitable imaging agents for detecting MRP-mediated d rug resistance in human cancers.