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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Honarvar H., Müller Cristina, Cohrs Susan, Haller Stephanie, Westerlund K., Karlstrom A. E., van der Meulen N. P., Schibli Roger, Tolmachev V.,
Project Translational molecular imaging of neuroendocrine tumours using innovative PET radionuclides
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Original article (peer-reviewed)

Journal Nuclear Medicine & Biology
Volume (Issue) 45
Page(s) 15 - 21
Title of proceedings Nuclear Medicine & Biology
DOI 10.1016/j.nucmedbio.2016.10.004


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)=68min) 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 4h post injection. Due to longer half-life, a positron-emitting radionuclide 44Sc (T(1/2)=4.04h) might be a preferable label for Affibody molecules for imaging at several hours after injection. METHODS: A synthetic second-generation anti-HER2 Affibody molecule ZHER2:2891 was labeled with 44Sc via a DOTA-chelator conjugated to the N-terminal amino group. Binding specificity, affinity and cellular processing 44Sc-DOTA-ZHER2:2891 and 68Ga-DOTA-ZHER2:2891 were compared in vitro using HER2-expressing cells. Biodistribution and imaging properties of 44Sc-DOTA-ZHER2:2891 and 68Ga-DOTA-ZHER2:2891 were evaluated in Balb/c nude mice bearing HER2-expression xenografts. RESULTS: The labeling yield of 98+/-2% and specific activity of 7.8GBq/mumol 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 3h post injection was similar for 44Sc-DOTA-ZHER2:2891 and 68Ga-DOTA-ZHER2:2891, but the blood clearance of the 44Sc-labeled variant was slower and the tumor-to-blood ratio was reduced (15+/-2 for 44Sc-DOTA-ZHER2:2891 vs 46+/-9 for 68Ga-DOTA-ZHER2:2891). At 6h after injection of 44Sc-DOTA-ZHER2:2891 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-ZHER2:2891 provides specific and high-contrast imaging of HER2-expressing xenografts. CONCLUSION: The 44Sc- DOTA-ZHER2:2891 Affibody molecule is a promising probe for imaging of HER2-expression in malignant