HAHAHA, HEHEHE, HIHIHI, or HKHKHK: Influence of position and composition of histidine containing tags on biodistribution of [99mTc(CO) 3]+-labeled affibody molecules

Camilla Hofström, Mohamed Altai, Hadis Honarvar, Joanna Strand, Jennie Malmberg, Seyed Jalal Hosseinimehr, Anna Orlova, Torbjörn Gräslund, Vladimir Tolmachev

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4966-4974
Number of pages9
JournalJournal of Medicinal Chemistry
Volume56
Issue number12
DOIs
Publication statusPublished - 27 Jun 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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