Affibody mediated tumor targeting of HER-2 expressing xenografts in mice
2006 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 33, no 6, 631-638 p.Article in journal (Refereed) Published
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.
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.
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.
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.
Place, publisher, year, edition, pages
2006. Vol. 33, no 6, 631-638 p.
affibody, HER-2, imaging, SKOV-3, tumour, breast-cancer, in-vitro, cellular retention, human tissues, antibody, proteins, binding, overexpression, localization, penetration
IdentifiersURN: urn:nbn:se:kth:diva-5179DOI: 10.1007/s00259-005-0012-3ISI: 000238023000002ScopusID: 2-s2.0-33646259546OAI: oai:DiVA.org:kth-5179DiVA: diva2:7987
Updated from submitted to published.
QC 201110072005-05-302005-05-302012-02-22Bibliographically approved