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Evaluation of the first (44)Sc-labeled Affibody molecule for imaging of HER2-expressing tumors.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. (Vladimir Tolmachev)
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2017 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 45, 15-21 p.Article in journal (Refereed) Published
Abstract [en]

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 (68)Ga (T½=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 (44)Sc (T½=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 (44)Sc via a DOTA-chelator conjugated to the N-terminal amino group. Binding specificity, affinity and cellular processing (44)Sc-DOTA-ZHER2:2891 and (68)Ga-DOTA-ZHER2:2891 were compared in vitro using HER2-expressing cells. Biodistribution and imaging properties of (44)Sc-DOTA-ZHER2:2891 and (68)Ga-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/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 3h post injection was similar for (44)Sc-DOTA-ZHER2:2891 and (68)Ga-DOTA-ZHER2:2891, but the blood clearance of the (44)Sc-labeled variant was slower and the tumor-to-blood ratio was reduced (15±2 for (44)Sc-DOTA-ZHER2:2891 vs 46±9 for (68)Ga-DOTA-ZHER2:2891). At 6h after injection of (44)Sc-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 (44)Sc-DOTA-ZHER2:2891 provides specific and high-contrast imaging of HER2-expressing xenografts.

CONCLUSION: The (44)Sc- DOTA-ZHER2:2891 Affibody molecule is a promising probe for imaging of HER2-expression in malignant tumors.

Place, publisher, year, edition, pages
2017. Vol. 45, 15-21 p.
National Category
Radiology, Nuclear Medicine and Medical Imaging
URN: urn:nbn:se:uu:diva-312076DOI: 10.1016/j.nucmedbio.2016.10.004PubMedID: 27837664OAI: oai:DiVA.org:uu-312076DiVA: diva2:1062156
Swedish Cancer SocietySwedish Research Council
Available from: 2017-01-04 Created: 2017-01-04 Last updated: 2017-01-09

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