HAHAHA, HEHEHE, HIHIHI, or HKHKHK: Influence of Position and Composition of Histidine Containing Tags on Biodistribution of [99mTc(CO)3]+-Labeled Affibody Molecules
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
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.
IdentifiersURN: urn:nbn:se:uu:diva-203052DOI: 10.1021/jm400218yISI: 000321237100012PubMedID: 23692562OAI: oai:DiVA.org:uu-203052DiVA: diva2:634902