Feasibility of imaging epcam expression in ovarian cancer using radiolabeled darpin ec1

Anzhelika Vorobyeva, Elena Konovalova, Tianqi Xu, Alexey Schulga, Mohamed Altai, Javad Garousi, Sara S. Rinne, Anna Orlova, Vladimir Tolmachev, Sergey Deyev

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Abstract

Epithelial cell adhesion molecule (EpCAM) is overexpressed in 55%–75% of ovarian carcinomas (OC). EpCAM might be used as a target for a treatment of disseminated OC. Designed ankyrin repeats protein (DARPin) Ec1 is a small (18 kDa) protein, which binds to EpCAM with subnanomolar affinity. We tested a hypothesis that Ec1 labeled with a non-residualizing label might serve as a companion imaging diagnostic for stratification of patients for EpCAM-targeting therapy. Ec1 was labeled with125I using N-succinimidyl-para-iodobenzoate. Binding affinity, specificity, and cellular processing of [125 I]I-PIB-Ec1 were evaluated using SKOV-3 and OVCAR-3 ovarian carcinoma cell lines. Biodistribution and tumor-targeting properties of [125 I]I-PIB-Ec1 were studied in Balb/c nu/nu mice bearing SKOV-3 and OVCAR-3 xenografts. EpCAM-negative Ramos lymphoma xenografts served as specificity control. Binding of [125 I]I-PIB-Ec1 to ovarian carcinoma cell lines was highly specific and had affinity in picomolar range. Slow internalization of [125 I]I-PIB-Ec1 by OC cells confirmed utility of non-residualizing label for in vivo imaging. [125I]I-PIB-Ec1 provided 6 h after injection tumor-to-blood ratios of 30 ± 11 and 48 ± 12 for OVCAR-3 and SKOV-3 xenografts, respectively, and high contrast to other organs. Tumor targeting was highly specific. Saturation of tumor uptake at a high dose of Ec1 in SKOV-3 model provided a rationale for dose selection in further studies using therapeutic conjugates of Ec1 for targeted therapy. In conclusion, [125I]I-PIB-Ec1 is a promising agent for visualizing EpCAM expression in OC.

Original languageEnglish
Article number3310
JournalInternational Journal of Molecular Sciences
Volume21
Issue number9
DOIs
Publication statusPublished - 1 May 2020

Keywords

  • Cancer
  • EpCAM
  • Iodine
  • Molecular imaging
  • Ovarian
  • PIB
  • Radionuclide
  • SPECT

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Vorobyeva, A., Konovalova, E., Xu, T., Schulga, A., Altai, M., Garousi, J., Rinne, S. S., Orlova, A., Tolmachev, V., & Deyev, S. (2020). Feasibility of imaging epcam expression in ovarian cancer using radiolabeled darpin ec1. International Journal of Molecular Sciences, 21(9), [3310]. https://doi.org/10.3390/ijms21093310