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Characterization of In-111 and Lu-177-labeled antibodies binding to CD44v6 using a novel automated radioimmunoassay
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
2008 (English)In: Journal of Molecular Recognition, ISSN 0952-3499, E-ISSN 1099-1352, Vol. 21, no 3, 179-183 p.Article in journal (Refereed) Published
Abstract [en]

Targeted cancer therapies rely on bifunctional molecules, typically a protein that specifically recognizes tumor cells and a toxic component which is linked to the protein. Therefore, development of such therapies includes detailed characterizations of protein-cell interactions in order to find a good targeting agent. Knowledge of factors such as antibody-antigen specificity, as well as cellular uptake, retention and affinity of the antibody are necessary in order to be successful. In this paper, we have used a novel instrument, LigandTracer (R) Yellow, to characterize the interactions of In-111 and Lu-177-labeled monoclonal antibodies (MAbs) with CD44v6. Uptake studies with varying specific radioactivity of the chimeric MAb U36 and with an irrelevant antibody for the CD44v6 receptor verified the reliability of the method, as well as the specificity of the antibody-receptor binding. Uptake, retention, and affinity were very similar for the In-111 and Lu-177-labeled conjugate, and were in line with earlier studies using manual methods. The fact that no adverse effects from labeling were seen, together with the high retention, could make these conjugates promising candidates for imaging and therapy of certain cancer types in the future. The novel LigandTracer technology reduced the workload and reagent spending while providing data with superior time resolution. The obtained results were in agreement with previously reported findings. In addition the real-time detection and higher time resolution made more detailed studies of the interactions possible.

Place, publisher, year, edition, pages
2008. Vol. 21, no 3, 179-183 p.
Keyword [en]
affinity, kinetics, medical imaging, targeted therapeutics, cancer
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-110053DOI: 10.1002/jmr.883ISI: 000256644300006PubMedID: 18438972OAI: oai:DiVA.org:uu-110053DiVA: diva2:275079
Available from: 2009-11-03 Created: 2009-11-02 Last updated: 2017-12-12Bibliographically approved

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Nestor, Marika

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