186Re-maSGS-ZHER2:342, a potential Affibody conjugate for systemic therapy of HER2-expressing tumours

Anna Orlova, Thuy A. Tran, Torun Ekblad, Amelie Eriksson Karlström, Vladimir Tolmachev

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)


Purpose: Affibody molecules are a novel class of tumour-targeting proteins, which combine small size (7 kDa) and picomolar affinities. The Affibody molecule ZHER2:342 has been suggested for imaging of HER2 expression in order to select patients for trastuzumab therapy. When optimizing chelators for 99mTc-labelling, we have found that synthetic Z HER2:342 conjugated with mercaptoacetyl-glycyl-glycyl-glycyl (maGGG) and mercaptoacetyl-glycyl-seryl-glycyl (maGSG) chelators provides relatively low renal uptake of radioactivity and could be suitable for therapy. Methods: maGGG-ZHER2:342 and maGSG-ZHER2:342 were labelled with 186Re and their biodistribution was studied in normal mice. Dosimetric evaluation and tumour targeting to HER2-overexpressed xenografts (SKOV-3) by 186Re-maGSG-ZHER2:342 were studied. Results: Gluconate-mediated labelling of maGGG-ZHER2:342 and maGSG-Z HER2:342 with 186Re provided a yield of more than 95% within 60 min. The conjugates were stable and demonstrated specific binding to HER2-expressing SKOV-3 cells. Biodistribution in normal mice demonstrated rapid blood clearance, low accumulation of radioactivity in the kidney and other organs, accumulating free perrhenate. Both 186Re-maGGG-Z HER2:342 and 186Re-maGSG-ZHER2:342 demonstrated lower renal uptake than their 99mTc-labelled counterparts. 186Re-maGSG-ZHER2:342 provided the lowest uptake in healthy tissues. Biodistribution of 186Re-maGSG-ZHER2:342 in nude mice bearing SKOV-3 xenografts showed specific targeting of tumours. Tumour uptake 24 h after injection (5.84±0.54%ID/g) exceeded the concentration in blood by more than 500-fold, and uptake in kidneys by about 8-fold. Preliminary dosimetric evaluation showed that dose-to-tumour should exceed dose-to-kidney by approximately 5-fold. Conclusion: Optimization of chelators improves biodistribution properties of rhenium-labelled small scaffold proteins and enables selection of promising radiotherapeutic agents based on the Affibody molecule.

Original languageEnglish
Pages (from-to)260-269
Number of pages10
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number2
Publication statusPublished - Feb 2010
Externally publishedYes


  • Affibody molecules
  • Chelator
  • HER2
  • Mercaptoacetyl
  • Rhenium

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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