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The use of closo-dodecaborate-containing linker improves targeting of HNSCC xenografts with radioiodinated chimeric monoclonal antibody U36
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 Surgical Sciences, Otolaryngology and Head and Neck Surgery.
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 Surgical Sciences, Otolaryngology and Head and Neck Surgery.
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2010 (English)In: Molecular Medicine Reports, ISSN 1791-2997, Vol. 3, no 1, 155-160 p.Article in journal (Refereed) Published
Abstract [en]

Radionuclide imaging of head and neck squamous cell carcinoma (HNSCC) using monoclonal antibodies (MAbs) has the potential to contribute to improved diagnosis and staging, thereby making more effective treatment possible. Chimeric monoclonal antibody U36 (cMAb U36), specific to CD44v6 antigen. is a candidate for the targeting of HNSCC. The aim of this study was to compare the influence of indirect iodination via closo-dodecaborate-based linker (DABI) with the influence of direct radioiodination on the biodistribution of the chimeric anti-CD44v6 antibody U36. The study was performed using nude mice bearing UT-SCC7 HNSCC xenografts using the paired-label method. The biodistribution of cMAb U36 labelled directly with I-131 and using DABI with I-125 was compared in the same animals. The influence of DABI on the tumour-to-organ ratio was evaluated. For both conjugates, radioactivity uptake in blood and organs decreased with time, except in tumours and the thyroid. DABI-labelled cMAb U36 was characterised by fast blood clearance and an elevated uptake in the liver and spleen. The use of DABI enabled a 1.5 to 2-fold improvement in the tumour-to-blood and tumour-to-organ ratios in comparison with direct radioiodination, with the exception of the liver and spleen. These results indicate that DABI is a promising linker for the coupling of radioiodine to HNSCC-targeting antibodies.

Place, publisher, year, edition, pages
2010. Vol. 3, no 1, 155-160 p.
Keyword [en]
nude mice, chimeric monoclonal antibody U36, head and neck squamous cell carcinoma, tumour transplantation, tumour targeting
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-127366DOI: 10.3892/mmr_00000233ISI: 000272753700023OAI: oai:DiVA.org:uu-127366DiVA: diva2:329676
Available from: 2010-07-13 Created: 2010-07-13 Last updated: 2015-02-27Bibliographically approved

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Engström, MatsEkberg, TomasNestor, MarikaAnniko, MattiTolmachev, Vladimir

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Otolaryngology and Head and Neck SurgeryDepartment of Oncology, Radiology and Clinical Immunology
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