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HAHAHA, HEHEHE, HIHIHI, or HKHKHK: Influence of Position and Composition of Histidine Containing Tags on Biodistribution of [99mTc(CO)3]+-Labeled Affibody Molecules
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Vladimir Tolmachev)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Vladimir Tolmachev)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Vladimir Tolmachev)
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2013 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 56, no 12, 4966-4974 p.Article in journal (Refereed) Published
Abstract [en]

Engineered affibody molecules can be used for high contrast in vivo molecular imaging. Extending a recombinantly produced HER2 binding affibody molecule with a hexa-histidine tag allows for convenient purification by immobilized metal-ion affinity chromatography and labeling with [99mTc(CO)3]+ but increases radioactivity uptake in the liver. To investigate the impact of charge, lipophilicity, and position on biodistribution, 10 variants of a histidine-based tag was attached to a HER2 binding affibody molecule. The biochemical properties and the HER2 binding affinity appeared to be similar for all variants. In vivo, positive charge promoted liver uptake. For N-terminally placed tags, lipophilicity promoted liver uptake and decreased kidney uptake. Kidney uptake was higher for C-terminally placed tags compared to their N-terminal counterparts. The variant with the amino acid composition HEHEHE placed in the N-terminus gave the lowest nonspecific uptake.

Place, publisher, year, edition, pages
2013. Vol. 56, no 12, 4966-4974 p.
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Basic Medicine
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URN: urn:nbn:se:uu:diva-203052DOI: 10.1021/jm400218yISI: 000321237100012PubMedID: 23692562OAI: oai:DiVA.org:uu-203052DiVA: diva2:634902
Available from: 2013-07-02 Created: 2013-07-02 Last updated: 2017-12-06Bibliographically approved

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Altai, MohamedHonarvar, HadisStrand, JoannaMalmberg, JennieHosseinimehr, Seyed JalalOrlova, AnnaTolmachev, Vladimir

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