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

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

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)631-638
Number of pages8
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume33
Issue number6
DOIs
Publication statusPublished - Jun 2006
Externally publishedYes

Keywords

  • Affibody
  • HER-2
  • Imaging
  • SKOV-3
  • Tumour

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Affibody-mediated tumour targeting of HER-2 expressing xenografts in mice'. Together they form a unique fingerprint.

Cite this