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Biodistribution of 211At labeled HER-2 binding affibody molecules in mice
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, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
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2007 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 17, no 5, 1141-1147 p.Article in journal (Refereed) Published
Abstract [en]

The size of affibody molecules makes them suitable as targeting agents for targeted radiotherapy with the alpha-emitter 211At, since their biokinetic properties match the short physical half-live of 211At. In this study, the potential for this approach was investigated in vivo. Two different HER-2 binding affibody molecules were radiolabeled with 211At using both the linker PAB (N-succinimidyl-para-astatobenzoate) and a decaborate-based linker, and the biodistribution in tumor-bearing nude mice was investigated. The influence of L-lysine and Na-thiocyanate on the 211At uptake in normal tissues was also studied. Based on the biokinetic information obtained, the absorbed dose was calculated for different organs. Compared with a previous biodistribution with 125I, the 211At biodistribution using the PAB linker showed higher uptake in lungs, stomach, thyroid and salivary glands, indicating release of free 211At. When the decaborate-based linker was used, the uptake in those organs was decreased, but instead, high uptake in kidneys and liver was found. The uptake, when using the PAB linker, could be significantly reduced in some organs by the use of L-lysine and/or Na-thiocyanate. In conclusion, affibody molecules have suitable blood-kinetics for targeted radionuclide therapy with 211At. However, the labeling chemistry affects the distribution in normal organs to a high degree and needs to be improved to allow clinical use.

Place, publisher, year, edition, pages
2007. Vol. 17, no 5, 1141-1147 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-104494ISI: 000245855800025PubMedID: 17390057OAI: oai:DiVA.org:uu-104494DiVA: diva2:219827
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-12-13Bibliographically approved

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Steffen, Ann-CharlottAlmqvist, YlvaLundqvist, HansTolmachev, VladimirCarlsson, Jörgen

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