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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)
Paul Scherrer Inst, Ctr Radiopharmaceut Sci ETH PSI USZ, Villigen, Switzerland.
Paul Scherrer Inst, Ctr Radiopharmaceut Sci ETH PSI USZ, Villigen, Switzerland.
Paul Scherrer Inst, Ctr Radiopharmaceut Sci ETH PSI USZ, Villigen, Switzerland.
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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.
Keyword [en]
Affibody molecule, Sc-44, DOTA, Z(HER2-2891), HER2, PET imaging
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-312076DOI: 10.1016/j.nucmedbio.2016.10.004ISI: 000392366900003PubMedID: 27837664OAI: oai:DiVA.org:uu-312076DiVA: diva2:1062156
Funder
Swedish Cancer Society, 2015/350 CAN2015/890Swedish Research Council, 2013-5135 2015-02353
Available from: 2017-01-04 Created: 2017-01-04 Last updated: 2017-02-24Bibliographically approved

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