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

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.

• Authors: Ann-Charlott Steffen, Anna Orlova, Maria Wikman, Fredrik Y Nilsson, Stefan Ståhl, Gregory P Adams, Vladimir Tolmachev, Jörgen Carlsson
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 33 Issue 6 Pg. 631-8 (Jun 2006) ISSN: 1619-7070 [Print] Germany
• PMID: 16538504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Radiopharmaceuticals
• Recombinant Fusion Proteins
• Z(HER2.4)2 affibody
• Receptor, ErbB-2

Topics

• Animals
• Cell Line, Tumor
• Drug Delivery Systems (methods)
• Female
• Humans
• Metabolic Clearance Rate
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Organ Specificity
• Ovarian Neoplasms (diagnostic imaging, metabolism)
• Radionuclide Imaging
• Radiopharmaceuticals (pharmacokinetics)
• Receptor, ErbB-2 (metabolism)
• Recombinant Fusion Proteins (pharmacokinetics)
• Tissue Distribution