Evaluation of the first Sc-44-labeled Affibody molecule for imaging of HER2-expressing tumors
2017 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 45, 15-21 p.Article in journal (Refereed) Published
Introduction: Affibody molecules are small (58 amino acids) high-affinity proteins based on a tri-helix nonimmunoglobulin scaffold. A clinical study has demonstrated that PET imaging using Affibody molecules labeled with Ga-68 (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 Sc-44 (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 Sc-44 via a DOTA-chelator conjugated to the N-terminal amino group. Binding specificity, affinity and cellular processing Sc-44-DOTA-Z(HER2:2891) and Ga-68-DOTA-Z(HER2:2891) were compared in vitro using HER2-expressing cells. Biodistribution and imaging properties of Sc-44-DOTA-Z(HER2,2891) and Ga-68-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/mu mol 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 Sc-44-DOTA-Z(HER2:2891) and Ga-68-DOTA-Z(HER2:2891), but the blood clearance of the Sc-44-labeled variant was slower and the tumor-to-blood ratio was reduced (15 +/- 2 for (SC)-S-44-DOTA-Z(HER2:2891) vs 46 +/- 9 for Ga-68-DOTA-Z(HER2.2891)). At 6 h after injection of Sc-44-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 (SC)-S-44-DOTA-ZHER2,2891 provides specific and high-contrast imaging of HER2-expressing xenografts. Conclusion: The Sc-44- DOTA-Z(HER2:2891) Affibody molecule is a promising probe for imaging of HER2-expression in malignant tumors.
Place, publisher, year, edition, pages
Elsevier, 2017. Vol. 45, 15-21 p.
Affibody molecule, Sc-44, DOTA, Z(HER2-2891), HER2, PET imaging
Radiology, Nuclear Medicine and Medical Imaging
IdentifiersURN: urn:nbn:se:kth:diva-202430DOI: 10.1016/j.nucmedbio.2016.10.004ISI: 000392366900003PubMedID: 27837664ScopusID: 2-s2.0-84994908259OAI: oai:DiVA.org:kth-202430DiVA: diva2:1078767
FunderSwedish Cancer Society, 2015/350Swedish Cancer Society, CAN2015/890Swedish Research Council, 2013-5135Swedish Research Council, 2015-02353
QC 201703062017-03-062017-03-062017-03-06Bibliographically approved