Skip to main content

Advertisement

Log in

Reduction of 99mTc-sestamibi and 99mTc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function

  • Short communication
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of 99mTc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, 99mTc-tetrofosmin (TF), was also examined. Cellular uptake of 99mTc-MIBI and 99mTc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N2 and 5% CO2 reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A, B
Fig. 2

References

  1. Ballinger JR. Imaging multidrug resistance with radiolabeled substrates for P-glycoprotein and multidrug resistance protein. Cancer Biother Radiopharm 2001; 16:1–7.

    CAS  PubMed  Google Scholar 

  2. Kuwano M, Uchiumi T, Hayakawa H, et al. The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies. Cancer Sci 2003; 94:9–14.

    CAS  PubMed  Google Scholar 

  3. Nishiyama Y, Yamamoto Y, Fukunaga K, et al. Evaluation of radiotherapeutic response in non-small cell lung cancer patients by technetium-99m MIBI and thallium-201 chloride SPET. Eur J Nucl Med 2000; 27:536–541.

    CAS  PubMed  Google Scholar 

  4. Moretti, J-L, Azaloux H, Boisseron D, Kouyoumdjian J-C, Vilcoq J. Primary breast cancer imaging with technetium-99m sestamibi and its relation with P-glycoprotein overexpression. Eur J Nucl Med 1996; 23:980–986.

    CAS  PubMed  Google Scholar 

  5. Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 2001; 93:266–276.

    CAS  PubMed  Google Scholar 

  6. Kinuya S, Yokoyama K, Li X-F, et al. Hypoxia-induced alteration of tracer accumulation in cultured cancer cells and xenografts in mice: implications for pre-therapeutic prediction of treatment outcomes with99mTc-sestamibi, 201Tl chloride and 99mTc-HL91. Eur J Nucl Med Mol Imaging 2002; 29:1006–1011.

    Article  CAS  PubMed  Google Scholar 

  7. Sakata K, Kwok TT, Murphy BJ, Laderoute KR, Gordon GR, Sutherland RM. Hypoxia-induced drug resistance: comparison to P-glycoprotein-associated drug resistance. Br J Cancer 1991; 64:809–814.

    CAS  PubMed  Google Scholar 

  8. Diah SK, Smitherman PK, Aldridge J, et al. Resistance of mitoxantrone in multidrug-resistant MCF7 breast cancer cells: evaluation of mitoxantrone transporter and the role of multidrug resistance protein family proteins. Cancer Res 2001; 61:5461–5467.

    CAS  PubMed  Google Scholar 

  9. Arbab AS, Koizumi K, Toyama K, Arai T, Araki T. Technetium-99m-tetrofosmin, technetium-99m-MIBI and thallium-201 uptake in rat myocardial cells. J Nucl Med 1998; 39:266–271.

    CAS  PubMed  Google Scholar 

  10. Sasaki M, Kuwabara Y, Ichiya Y, et al. Prediction of the chemosensitivity of lung cancer by99mTc-hexakis-2-methoxyisobutyl isonitrile SPECT. J Nucl Med 1999; 40:1778–1783.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Seigo Kinuya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kinuya, S., Li, XF., Yokoyama, K. et al. Reduction of 99mTc-sestamibi and 99mTc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function. Eur J Nucl Med Mol Imaging 30, 1529–1531 (2003). https://doi.org/10.1007/s00259-003-1268-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-003-1268-0

Keywords

Navigation