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Tumor imaging using a picomolar affinity HER2 binding affibody molecule
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.ORCID iD: 0000-0001-6120-2683
Affibody AB.
Affibody AB.
Affibody AB.
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2006 (English)In: Cancer Research, ISSN 0008-5472, Vol. 66, no 8, 4339-48 p.Article in journal (Refereed) Published
Abstract [en]

The detection of cell-bound proteins that are produced due to aberrant gene expression in malignant tumors can provide important diagnostic information influencing patient management. The use of small radiolabeled targeting proteins would enable high-contrast radionuclide imaging of cancers expressing such antigens if adequate binding affinity and specificity could be provided. Here, we describe a HER2-specific 6 kDa Affibody molecule (hereinafter denoted Affibody molecule) with 22 pmol/L affinity that can be used for the visualization of HER2 expression in tumors in vivo using gamma camera. A library for affinity maturation was constructed by re-randomization of relevant positions identified after the alignment of first-generation variants of nanomolar affinity (50 nmol/L). One selected Affibody molecule, Z(HER2:342) showed a >2,200-fold increase in affinity achieved through a single-library affinity maturation step. When radioiodinated, the affinity-matured Affibody molecule showed clear, high-contrast visualization of HER2-expressing xenografts in mice as early as 6 hours post-injection. The tumor uptake at 4 hours post-injection was improved 4-fold (due to increased affinity) with 9% of the injected dose per gram of tissue in the tumor. Affibody molecules represent a new class of affinity molecules that can provide small sized, high affinity cancer-specific ligands, which may be well suited for tumor imaging.

Place, publisher, year, edition, pages
2006. Vol. 66, no 8, 4339-48 p.
Keyword [en]
Cancer, Tumor, Radiation, Therapy
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-104475DOI: 10.1158/0008-5472.CAN-05-3521PubMedID: 16618759OAI: oai:DiVA.org:uu-104475DiVA: diva2:219868
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2015-03-24Bibliographically approved

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Orlova, AnnaTolmachev, Vladimir
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