Evaluation of the first &lt;sup&gt;44&lt;/sup&gt;Sc-labeled Affibody molecule for imaging of HER2-expressing tumors

Honarvar, Hadis; Müller, Cristina; Cohrs, Susan; Haller, Stephanie; Westerlund, Kristina; Eriksson Karlström, Amelie; van der Meulen, Nicholas P.; Schibli, Roger; Tolmachev, Vladimir

doi:10.1016/j.nucmedbio.2016.10.004

Evaluation of the first ⁴⁴Sc-labeled Affibody molecule for imaging of HER2-expressing tumors

Honarvar H, Müller C, Cohrs S, Haller S, Westerlund K, Eriksson Karlström A, van der Meulen NP, Schibli R & Tolmachev V

Citation

Honarvar, H., Müller, C., Cohrs, S., Haller, S., Westerlund, K., Eriksson Karlström, A., … Tolmachev, V. (2017). Evaluation of the first ⁴⁴Sc-labeled Affibody molecule for imaging of HER2-expressing tumors. Nuclear Medicine and Biology, 45, 15-21. https://doi.org/10.1016/j.nucmedbio.2016.10.004

Persistent URL https://www.dora.lib4ri.ch/psi/islandora/object/psi:4218

Introduction: Affibody molecules are small (58 amino acids) high-affinity proteins based on a tri-helix non-immunoglobulin scaffold. A clinical study has demonstrated that PET imaging using Affibody molecules labeled with ⁶⁸Ga (T_1⁄2 = 68 min) can visualize metastases of breast cancer expressing human epidermal growth factor receptor type 2 (HER2) and provide discrimination between tumors with high and low expression level. This may help to identify breast cancer patients benefiting from HER2-targeting therapies. The best discrimination was at 4 h post injection. Due to longer half-life, a positron-emitting radionuclide ⁴⁴Sc (T_1⁄2 = 4.04 h) might be a preferable label for Affibody molecules for imaging at several hours after injection.
Methods: A synthetic second-generation anti-HER2 Affibody molecule Z_HER2:2891 was labeled with ⁴⁴Sc via a DOTA-chelator conjugated to the N-terminal amino group. Binding specificity, affinity and cellular processing ⁴⁴Sc-DOTA-Z_HER2:2891 and ⁶⁸Ga-DOTA-Z_HER2:2891 were compared in vitro using HER2-expressing cells. Biodistribution and imaging properties of ⁴⁴Sc-DOTA-Z_HER2:2891 and ⁶⁸Ga-DOTA-Z_HER2:2891 were evaluated in Balb/c nude mice bearing HER2-expression xenografts.
Results: The labeling yield of 98 ± 2% and specific activity of 7.8 GBq/μmol were obtained. The conjugate demonstrated specific binding to HER2-expressing SKOV3.ip cells in vitro and to SKOV3.ip xenografts in nude mice. The distribution of radioactivity at 3 h post injection was similar for ⁴⁴Sc-DOTA-Z_HER2:2891 and ⁶⁸Ga-DOTA-Z_HER2:2891, but the blood clearance of the ⁴⁴Sc-labeled variant was slower and the tumor-to-blood ratio was reduced (15 ± 2 for ⁴⁴Sc-DOTA-Z_HER2:2891 vs 46 ± 9 for ⁶⁸Ga-DOTA-Z_HER2:2891). At 6 h after injection of ⁴⁴Sc-DOTA-Z_HER2:2891 the tumor uptake was 8 ± 2% IA/g and the tumor-to-blood ratio was 51 ± 8. Imaging using small-animal PET/CT demonstrated that ⁴⁴Sc-DOTA-Z_HER2:2891 provides specific and high-contrast imaging of HER2-expressing xenografts.
Conclusion: The ⁴⁴Sc- DOTA-Z_HER2:2891 Affibody molecule is a promising probe for imaging of HER2-expression in malignant tumors.