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
Affiliations
Anzhelika Vorobyeva
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
Ekaterina Bezverkhniaia
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, Russia
Elena Konovalova
Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
Alexey Schulga
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, Russia
Javad Garousi
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
Olga Vorontsova
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
Ayman Abouzayed
Department of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, Sweden
Anna Orlova
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, Russia
Sergey Deyev
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, Russia
Vladimir Tolmachev
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
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.
