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

• Published in: European Journal of Nuclear Medicine Vol. 27; no. 12; pp. 1786 - 1792
• Main Authors: UTSUNOMIYA, Keita, BALLINGER, James R, PIQUETTE-MILLER, Micheline, RAUTH, Andrew M, TANG, Wendy, SU, Zi-Fen, ICHISE, Masanori
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.12.2000; Springer Nature B.V
• Subjects: ATP Binding Cassette Transporter, Subfamily B - metabolism; ATP Binding Cassette Transporter, Subfamily B, Member 1 - biosynthesis; Biological and medical sciences; Carcinoma - genetics; Carcinoma - metabolism; Contrast media. Radiopharmaceuticals; Genes, MDR - genetics; Humans; Indicators and Reagents; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Miscellaneous. Technology; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - metabolism; Organophosphorus Compounds - pharmacokinetics; Organotechnetium Compounds - pharmacokinetics; Pharmacology. Drug treatments; Radionuclide investigations; Radiopharmaceuticals - pharmacokinetics; Reverse Transcriptase Polymerase Chain Reaction; Technetium Tc 99m Sestamibi - pharmacokinetics; Tumor Cells, Cultured; Antineoplastic agent; Radionuclide study; Human; Cell culture; Nasopharynx; Malignant tumor; Experimental study; Binding protein; Reaction medium; ENT disease; Medical imagery; Pharynx disease; Pharmacokinetics; Technetium(99mTc) sestamibi; Medical application; Comparative study
• ISSN: 0340-6997; 1619-7070; 1619-7089
• 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.