Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with 188Re

Mohamed Altai, Hadis Honarvar, Helena Wallberg, Joanna Strand, Zohreh Varasteh, Maria Rosestedt, Anna Orlova, Finn Dunas, Mattias Sandström, John Löfblom, Vladimir Tolmachev, Stefan Stahl

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of 188Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all 188Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The 188Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of 188Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental 188Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of 188Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.

Original languageEnglish
Pages (from-to)519-528
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 24 Nov 2014
Externally publishedYes


  • Affibody
  • Biodistribution
  • HER2
  • Peptide-based chelator
  • Radionuclide therapy
  • Rhenium-188

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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