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European Journal of Nuclear Medicine and Molecular Imaging

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01.06.2006 | Original article

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

verfasst von: Ann-Charlott Steffen, Anna Orlova, Maria Wikman, Fredrik Y. Nilsson, Stefan Ståhl, Gregory P. Adams, Vladimir Tolmachev, Jörgen Carlsson

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 6/2006

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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 (Z_HER2:4)₂, with potential for such applications. The (Z_HER2:4)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 (Z_HER2:4)₂ affibody was studied in nude mice carrying tumours from xenografted HER-2 overexpressing SKOV-3 cells.

Results

The radioiodinated (Z_HER2:4)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 (Z_HER2:4)₂ affibody is an interesting candidate for applications in nuclear medicine, such as radionuclide-based tumour imaging and therapy.

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Titel: Affibody-mediated tumour targeting of HER-2 expressing xenografts in mice
verfasst von: Ann-Charlott Steffen
Anna Orlova
Maria Wikman
Fredrik Y. Nilsson
Stefan Ståhl
Gregory P. Adams
Vladimir Tolmachev
Jörgen Carlsson
Publikationsdatum: 01.06.2006
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 6/2006
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-005-0012-3

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

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

Abstract

Purpose

Methods

Results

Conclusion

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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