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

Catarina Xavier, Ilse Vaneycken, Matthias D'huyvetter, Johannes Heemskerk, Marleen Keyaerts, Cécile Vincke, Nick Devoogdt, Serge Muyldermans, Tony Lahoutte, Vicky Caveliers, An Aerts, Nathalie Impens, Sarah Baatout

    Research outputpeer-review


    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
    StatePublished - 13 May 2013

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