Synthesis, Preclinical Validation, Dosimetry, and Toxicity of 68Ga-NOTA-Anti-HER2 Nanobodies for iPET Imaging of HER2 Receptor Expression in Cancer

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  • Catarina Xavier
  • Ilse Vaneycken
  • Matthias D'huyvetter
  • Johannes Heemskerk
  • Marleen Keyaerts
  • Cécile Vincke
  • Nick Devoogdt
  • Serge Muyldermans
  • Tony Lahoutte
  • Vicky Caveliers

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Nanobodies are the smallest fully functional antigen-binding antibody fragments possessing ideal properties as probes for molecular imaging. In this study we labeled the anti–human epidermal growth factor receptor type 2 (HER2) Nanobody with 68Ga via a 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) derivative and assessed its use for HER2 iPET imaging. Methods: The 2Rs15dHis6 Nanobody and the lead optimized current-good-manufacturing-practice grade analog 2Rs15d were conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7- triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) to enable fast and efficient 68Ga labeling. Biodistribution and PET/CT studies were performed on HER2-positive and -negative tumor xenografts. The effect of injected mass on biodistribution was evaluated. The biodistribution data were extrapolated to calculate radiation dose estimates for the adult female using OLINDA software. A single-dose extended-toxicity study for NOTA- 2Rs15d was performed on healthy mice up to a dose of 10 mg/kg.


Original languageEnglish
Pages (from-to)776-784
JournalJournal of Nuclear Medicine
Issue number5
Publication statusPublished - 13 May 2013


  • HER2, breast cancer, nanobody, iPET

ID: 258653