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

Eur J Nucl Med. 2000 Dec;27(12):1786-92. doi: 10.1007/s002590000375.


The potential clinical use of technetium-99m labeled sestamibi (Tc-MIBI) and 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 nasopharyngeal carcinoma cell line CNE-1 were examined in the presence or absence of various inhibitors of P-glycoprotein (PGP) and/or multidrug resistance associated protein (MRP) activity [GG918, PSC833, verapamil (Vrp), cyclosporin A (CsA) and buthionine sulfoximine (BSO)]. Reverse-transcriptase polymerase chain reaction analysis and immunodetection of the CNE-1 cells detected expression of MRP, MRPI and MRP2 but not PGP. Tc-MIBI and Tc-Tfos accumulation was increased (P < 0.0001) and efflux decreased (P < 0.05) in the presence of BSO, CsA, Vrp and PSC833 but not GG918, which is a specific inhibitor of PGP. The absolute accumulation of Tc-MIBI was approximately twofold higher than that seen with Tc-Tfos, whereas the addition of inhibitors caused a much greater suppression of Tc-Tfos transport (>2 times greater than for Tc-MIBI). However, no qualitative differences in inhibitors were seen between 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 BSO but not GG918 can inhibit MRP activity. These results indicate that Tc-MIBI and Tc-Tfos may be suitable imaging agents for detecting MRP-mediated drug resistance in human cancers.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Genes, MDR / genetics
  • Humans
  • Indicators and Reagents
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Organophosphorus Compounds / pharmacokinetics*
  • Organotechnetium Compounds / pharmacokinetics*
  • Radiopharmaceuticals / pharmacokinetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Technetium Tc 99m Sestamibi / pharmacokinetics*
  • Tumor Cells, Cultured


  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Indicators and Reagents
  • Organophosphorus Compounds
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • technetium tc-99m tetrofosmin
  • Technetium Tc 99m Sestamibi