Molecular design of HER3-targeting affibody molecules: Influence of chelator and presence of HEHEHE-Tag on biodistribution of 68 Ga-labeled tracers

Charles Dahlsson Leitao, Sara S. Rinne, Bogdan Mitran, Anzhelika Vorobyeva, Ken G. Andersson, Vladimir Tolmachev, Stefan Ståhl, John Löfblom, Anna Orlova

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Affibody-based imaging of HER3 is a promising approach for patient stratification. We investigated the influence of a hydrophilic HEHEHE-tag ((HE) 3 -tag) and two different gallium-68/chelator-complexes on the biodistribution of Z 08698 with the aim to improve the tracer for PET imaging. Affibody molecules (HE) 3 -Z 08698 -X and Z 08698 -X (X = NOTA, NODAGA) were produced and labeled with gallium-68. Binding specificity and cellular processing were studied in HER3-expressing human cancer cell lines BxPC-3 and DU145. Biodistribution was studied 3 h p.i. in Balb/c nu/nu mice bearing BxPC-3 xenografts. Mice were imaged 3 h p.i. using microPET/CT. Conjugates were stably labeled with gallium-68 and bound specifically to HER3 in vitro and in vivo. Association to cells was rapid but internalization was slow. Uptake in tissues, including tumors, was lower for (HE) 3 -Z 08698 -X than for non-tagged variants. The neutral [ 68 Ga]Ga-NODAGA complex reduced the hepatic uptake of Z 08698 compared to positively charged [ 68 Ga]Ga-NOTA-conjugated variants. The influence of the chelator was more pronounced in variants without (HE) 3- tag. In conclusion, hydrophilic (HE) 3 -tag and neutral charge of the [ 68 Ga]Ga-NODAGA complex promoted blood clearance and lowered hepatic uptake of Z 08698 . [ 68 Ga]Ga-(HE) 3 -Z 08698 -NODAGA was considered most promising, providing the lowest blood and hepatic uptake and the best imaging contrast among the tested variants.

Original languageEnglish
Article number1080
JournalInternational Journal of Molecular Sciences
Issue number5
Publication statusPublished - Mar 2019
Externally publishedYes


  • Affibody
  • Gallium-68
  • HER3
  • Molecular imaging
  • NOTA
  • PET

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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