Effects of lysine-containing mercaptoacetyl-based chelators on the biodistribution of 99mTc-labeled anti-HER2 affibody molecules

Thuy A. Tran, Torun Ekblad, Anna Orlova, Mattias Sandström, Joachim Feldwisch, Anders Wennborg, Lars Abrahmsén, Vladimir Tolmachev, Amelie Eriksson Karlström

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


The effects of polar (mercaptoacetyl-triseryl) and negatively charged (mercaptoacetyl-triglumatyl) chelators on the biodistribution of 99mTc-labeled anti-HER2 Affibody molecules were previously investigated. With glycine, serine, and glutamate, we demonstrated that substitution with a single amino acid in the chelator can significantly influence the biodistribution properties and the excretion pathways. Here, we have taken this investigation further, by analyzing the effects of introduction of a positive amino acid residue on the in vivo properties of the 99mTc-labeled Affibody molecule. The Affibody molecules with mercaptoacetyl-seryl-lysyl-seryl (maSKS) and mercaptoacetyl-trilysyl (maKKK) extensions were produced by peptide synthesis and labeled with 99mTc in alkaline conditions. A comparative biodistribution was performed in normal mice to evaluate the excretion pathway. A shift toward renal excretion was obtained when serine was substituted with lysine in the chelating sequence. The radioactivity in the gastrointestinal tract was reduced 3-fold for the 99mTc-maSKS-ZHER2:342 and 99mTc-maKKK-Z HER2:342 in comparison with the 99mTc-maSSS- Z HER2:342 conjugate 4 h post injection (p.i.). The radioactivity in the liver was elevated when a triple substitution of positively charged lysine was used. The tumor targeting properties of 99mTc-maSKS-Z HER2:342 were further investigated in SKOV-3 xenografts. The tumor uptake of 99mTc-maSKS-ZHER2:342 was 17 ± 7% IA/g 4 h p.i. Tumor xenografts were well-visualized by gamma scintigraphy. In conclusion, the substitution with one single lysine in the chelator results in better tumor imaging properties of the Affibody molecule ZHER2:342 and is favorable for imaging of tumors and metastases in the abdominal area. Multiple lysine residues in the chelator are, however, undesirable due to elevated uptake both in the liver and kidneys.

Original languageEnglish
Pages (from-to)2568-2576
Number of pages9
JournalBioconjugate Chemistry
Issue number12
Publication statusPublished - 17 Dec 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Effects of lysine-containing mercaptoacetyl-based chelators on the biodistribution of <sup>99m</sup>Tc-labeled anti-HER2 affibody molecules'. Together they form a unique fingerprint.

Cite this