Radionuclide molecular imaging of EpCAM expression in triple-negative breast cancer using the scaffold protein DARPin Ec1

Anzhelika Vorobyeva, Ekaterina Bezverkhniaia, Elena Konovalova, Alexey Schulga, Javad Garousi, Olga Vorontsova, Ayman Abouzayed, Anna Orlova, Sergey Deyev, Vladimir Tolmachev

Research output: Contribution to journalArticlepeer-review

Abstract

Efficient treatment of disseminated triple-negative breast cancer (TNBC) remains an unmet clinical need. The epithelial cell adhesion molecule (EpCAM) is often overexpressed on the surface of TNBC cells, which makes EpCAM a potential therapeutic target. Radionuclide molecular imaging of EpCAM expression might permit selection of patients for EpCAM-targeting therapies. In this study, we evaluated a scaffold protein, designed ankyrin repeat protein (DARPin) Ec1, for imaging of EpCAM in TNBC. DARPin Ec1 was labeled with a non-residualizing [125I]I-para-iodobenzoate (PIB) label and a residualizing [99mTc]Tc(CO)3 label. Both imaging probes retained high binding specificity and affinity to EpCAM-expressing MDA-MB-468 TNBC cells after labeling. Internalization studies showed that Ec1 was retained on the surface of MDA-MB-468 cells to a high degree up to 24 h. Biodistribution in Balb/c nu/nu mice bearing MDA-MB-468 xenografts demonstrated specific uptake of both [125I]I-PIB-Ec1 and [99mTc]Tc(CO)3-Ec1 in TNBC tumors. [125I]I-PIB-Ec1 had appreciably lower uptake in normal organs compared with [99mTc]Tc(CO)3-Ec1, which resulted in significantly (p < 0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by micro-Single-Photon Emission Computed Tomography/Computed Tomography (microSPECT/CT) imaging. In conclusion, an indirectly radioiodinated Ec1 is the preferable probe for imaging of EpCAM in TNBC.

Original languageEnglish
Article number4719
JournalMolecules
Volume25
Issue number20
DOIs
Publication statusPublished - Oct 2020

Keywords

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

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Radionuclide molecular imaging of EpCAM expression in triple-negative breast cancer using the scaffold protein DARPin Ec1'. Together they form a unique fingerprint.

Cite this