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Affibody-mediated tumour targeting of HER-2 expressing xenografts in mice

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

Abstract

Purpose

Targeted delivery of radionuclides for diagnostic and therapeutic applications has until recently largely been limited to receptor ligands, antibodies and antibody-derived molecules. Here, we present a new type of molecule, a 15-kDa bivalent affibody called (ZHER2:4)2, with potential for such applications. The (ZHER2:4)2 affibody showed high apparent affinity (K D=3 nM) towards the oncogene product HER-2 (also called p185/neu or c-erbB-2), which is often overexpressed in breast and ovarian cancers. The purpose of this study was to investigate the in vivo properties of the new targeting agent.

Methods

The biodistribution and tumour uptake of the radioiodinated (ZHER2:4)2 affibody was studied in nude mice carrying tumours from xenografted HER-2 overexpressing SKOV-3 cells.

Results

The radioiodinated (ZHER2:4)2 affibody was primarily excreted through the kidneys, and significant amounts of radioactivity were specifically targeted to the tumours. The blood-borne radioactivity was, at all times, mainly in the macromolecular fraction. A tumour-to-blood ratio of about 10:1 was obtained 8 h post injection, and the tumours could be easily visualised with a gamma camera at this time point.

Conclusion

The results indicate that the (ZHER2:4)2 affibody is an interesting candidate for applications in nuclear medicine, such as radionuclide-based tumour imaging and therapy.

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Acknowledgements

The authors thank Charles Widström at the department of Nuclear Medicine at Uppsala University Hospital for help with the gamma camera. Thanks also to Kenneth Wester and Veronika Asplund Eriksson for help with the immunohistochemistry, autoradiography and photographic procedures. The work was financially supported by grant no 0980-B04-17XCC (040171) from the Swedish Cancer Society.

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Authors and Affiliations

  1. Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

    Ann-Charlott Steffen, Fredrik Y. Nilsson, Vladimir Tolmachev & Jörgen Carlsson

  2. Affibody AB, Bromma, Sweden

    Anna Orlova & Fredrik Y. Nilsson

  3. Department of Molecular Biotechnology, AlbaNova University Center, Royal Institute of Technology (KTH), Stockholm, Sweden

    Maria Wikman & Stefan Ståhl

  4. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA

    Gregory P. Adams

Authors
  1. Ann-Charlott Steffen
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  2. Anna Orlova
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  3. Maria Wikman
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  4. Fredrik Y. Nilsson
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  5. Stefan Ståhl
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  6. Gregory P. Adams
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  7. Vladimir Tolmachev
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  8. Jörgen Carlsson
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Correspondence to Ann-Charlott Steffen.

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Steffen, AC., Orlova, A., Wikman, M. et al. Affibody-mediated tumour targeting of HER-2 expressing xenografts in mice. Eur J Nucl Med Mol Imaging 33, 631–638 (2006). https://doi.org/10.1007/s00259-005-0012-3

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  • DOI: https://doi.org/10.1007/s00259-005-0012-3

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