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.
|Number of pages||8|
|Journal||European Journal of Nuclear Medicine and Molecular Imaging|
|Publication status||Published - Jun 2006|
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging