Pharmaceutical Research

, 36:18 | Cite as

Different Efflux Transporter Affinity and Metabolism of 99mTc-2-Methoxyisobutylisonitrile and 99mTc-Tetrofosmin for Multidrug Resistance Monitoring in Cancer

  • Masato KobayashiEmail author
  • Takafumi Tsujiuchi
  • Yuya Okui
  • Asuka Mizutani
  • Kodai Nishi
  • Takeo Nakanishi
  • Ryuichi Nishii
  • Kazuki Fukuchi
  • Ikumi Tamai
  • Keiichi Kawai
Research Paper



Little is known about the affinity and stability of 99mTc-labeled 2-methoxyisobutylisonitrile (99mTc-MIBI) and tetrofosmin (99mTc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of 99mTc-labeled compounds for these transporters and their stability.


99mTc-MIBI and 99mTc-TF were incubated in vesicles expressing P-glycoprotein (MDR1), multidrug resistance-associated protein (MRP)1–4, or breast cancer resistance protein with and without verapamil (MDR1 inhibitor) or MK-571 (MRP inhibitor). Time activity curves of 99mTc-labeled compounds were established using SK-N-SH neuroblastoma, SK-MEL-28 melanoma, and PC-3 prostate adenocarcinoma cell lines, and transporter expression of multiple drug resistance was measured in these cells. The stability was evaluated.


In vesicles, 99mTc-labeled compounds had affinity for MDR1 and MRP1. 99mTc-TF had additional affinity for MRP2 and MRP3. In SK-N-SH cells expressing MDR1 and MRP1, MK-571 produced the highest uptake of both 99mTc-labeled compounds. 99mTc-MIBI uptake with inhibitors was higher than 99mTc-TF uptake with inhibitors. 99mTc-TF was taken up more in SK-MEL-28 cells expressing MRP1 and MRP2 than PC-3 cells expressing MRP1 and MRP3. 99mTc-MIBI was metabolized, whereas 99mTc-TF had high stability.


99mTc-MIBI is exported via MDR1 and MRP1 (MRP1 > MDR1) at greater levels and more quickly compared to 99mTc-TF, which is exported via MDR1 and MRP1–3 (MRP1 > MDR1; MRP1, 2 > MRP3). Because 99mTc-MIBI is metabolized, clinical imaging for monitoring MDR and shorter examination times may be possible with an earlier scanning time on late phase imaging. 99mTc-TF has high stability and accurately reflects the function of MDR1 and MRP1–3.


99mTc-MIBI 99mTc-tetrofosmin adenosine triphosphate-binding cassette transporters multidrug resistance multidrug resistance-associated protein 



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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Masato Kobayashi
    • 1
    Email author
  • Takafumi Tsujiuchi
    • 2
  • Yuya Okui
    • 2
  • Asuka Mizutani
    • 2
  • Kodai Nishi
    • 3
  • Takeo Nakanishi
    • 4
  • Ryuichi Nishii
    • 5
  • Kazuki Fukuchi
    • 6
  • Ikumi Tamai
    • 4
  • Keiichi Kawai
    • 2
    • 7
  1. 1.Wellness Promotion Science Center, Institute of Medical, Pharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan
  2. 2.School of Health Sciences, Institute of Medical, Pharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan
  3. 3.Department of Radioisotope Medicine Atomic Bomb Disease InstituteNagasaki UniversityNagasakiJapan
  4. 4.School of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan
  5. 5.Department of Molecular Imaging and TheranosticsNational Institute of Radiological SciencesChibaJapan
  6. 6.Graduate School of Medicine, Division of Health SciencesOsaka UniversityOsakaJapan
  7. 7.Biomedical Imaging Research CenterUniversity of FukuiFukuiJapan

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