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Is MIBG a substrate of P-glycoprotein?

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Radionuclide therapy with 131I-labelled meta-iodobenzylguanidine ([131I]MIBG) is effective in cases where it is difficult to carry out surgical resection or debulking of neuroendocrine tumours (NETs). However, it has recently been reported that P-glycoprotein (P-gp) is expressed in these NETs. Therefore, it is important to clarify whether MIBG is a substrate of P-gp or not. In this study, using a human cell line which overexpresses P-gp, LLC-GA5-COL150, we investigated this question.

Methods

The transcellular transport and accumulation of [125I]MIBG were measured using monolayer cultures grown in Transwell chambers. [125I]MIBG was added to either the basolateral or the apical side, aliquots of the incubation medium on the other side were taken at specified times, and the radioactivity was measured. For accumulation experiments, the cells on the filters were solubilised and the radioactivity in aliquots was measured.

Results

There were no significant differences in the transport of MIBG between LLC-PK1 and LLC-GA5-COL150 monolayers in either direction until 60 min. With respect to the accumulation of MIBG, there were no significant differences between LLC-PK1 and LLC-GA5-COL150 cells in either direction.

Conclusion

MIBG is not a substrate of P-gp. Therefore, radionuclide therapy with MIBG would be useful in the treatment of NETs expressing P-gp.

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Acknowledgements

We would like to thank Daiichi Radioisotope Laboratories Ltd., Tokyo, Japan, for providing [125I]MIBG. This study was supported in part by Grants-in-aid for General Scientific Research from the Ministry of Education, Culture, Sports, and Science.

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Authors and Affiliations

  1. Radioisotopes Research Laboratory, Faculty of Medicine, Kyoto University Hospital, Kyoto University, Kyoto, Japan

    Yasushi Kiyono

  2. Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Tomoko Yamashita, Hisako Doi, Yuji Kuge & Hideo Saji

  3. Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital, Kyoto University, Sakyo-ku, Kyoto, Japan

    Toshiya Katsura & Ken-Ichi Inui

Authors
  1. Yasushi Kiyono
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  2. Tomoko Yamashita
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  3. Hisako Doi
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  4. Yuji Kuge
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  5. Toshiya Katsura
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  6. Ken-Ichi Inui
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  7. Hideo Saji
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Correspondence to Hideo Saji.

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Kiyono, Y., Yamashita, T., Doi, H. et al. Is MIBG a substrate of P-glycoprotein?. Eur J Nucl Med Mol Imaging 34, 448–452 (2007). https://doi.org/10.1007/s00259-006-0256-6

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  • DOI: https://doi.org/10.1007/s00259-006-0256-6

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