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

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

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

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 (T½ = 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 (T½ = 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 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 7.8 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-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 6 h 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 tumors.

Original languageEnglish
Pages (from-to)15-21
Number of pages7
JournalNuclear Medicine and Biology
Volume45
DOIs
Publication statusPublished - 1 Feb 2017
Externally publishedYes

Keywords

  • Sc
  • Affibody molecule
  • DOTA
  • HER2
  • PET imaging
  • Z

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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