Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1
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 expres...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/20/4719 |
| _version_ | 1827704308234190848 |
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| author | Anzhelika Vorobyeva Ekaterina Bezverkhniaia Elena Konovalova Alexey Schulga Javad Garousi Olga Vorontsova Ayman Abouzayed Anna Orlova Sergey Deyev Vladimir Tolmachev |
| author_facet | Anzhelika Vorobyeva Ekaterina Bezverkhniaia Elena Konovalova Alexey Schulga Javad Garousi Olga Vorontsova Ayman Abouzayed Anna Orlova Sergey Deyev Vladimir Tolmachev |
| author_sort | Anzhelika Vorobyeva |
| collection | DOAJ |
| description | 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 [<sup>125</sup>I]I-<i>para</i>-iodobenzoate (PIB) label and a residualizing [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub> 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 [<sup>125</sup>I]I-PIB-Ec1 and [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-Ec1 in TNBC tumors. [<sup>125</sup>I]I-PIB-Ec1 had appreciably lower uptake in normal organs compared with [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-Ec1, which resulted in significantly (<i>p</i> < 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. |
| first_indexed | 2024-03-10T15:37:50Z |
| format | Article |
| id | doaj.art-c156c6384f714624808c4eba38498ace |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:37:50Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c156c6384f714624808c4eba38498ace2023-11-20T17:07:59ZengMDPI AGMolecules1420-30492020-10-012520471910.3390/molecules25204719Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1Anzhelika Vorobyeva0Ekaterina Bezverkhniaia1Elena Konovalova2Alexey Schulga3Javad Garousi4Olga Vorontsova5Ayman Abouzayed6Anna Orlova7Sergey Deyev8Vladimir Tolmachev9Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, SwedenResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, RussiaMolecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, RussiaDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, SwedenDepartment of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, SwedenResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, RussiaResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, RussiaDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, SwedenEfficient 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 [<sup>125</sup>I]I-<i>para</i>-iodobenzoate (PIB) label and a residualizing [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub> 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 [<sup>125</sup>I]I-PIB-Ec1 and [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-Ec1 in TNBC tumors. [<sup>125</sup>I]I-PIB-Ec1 had appreciably lower uptake in normal organs compared with [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-Ec1, which resulted in significantly (<i>p</i> < 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.https://www.mdpi.com/1420-3049/25/20/4719EpCAMradionuclidemolecular imagingSPECTiodinePIB |
| spellingShingle | Anzhelika Vorobyeva Ekaterina Bezverkhniaia Elena Konovalova Alexey Schulga Javad Garousi Olga Vorontsova Ayman Abouzayed Anna Orlova Sergey Deyev Vladimir Tolmachev Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1 Molecules EpCAM radionuclide molecular imaging SPECT iodine PIB |
| title | Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1 |
| title_full | Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1 |
| title_fullStr | Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1 |
| title_full_unstemmed | Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1 |
| title_short | Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1 |
| title_sort | radionuclide molecular imaging of epcam expression in triple negative breast cancer using the scaffold protein darpin ec1 |
| topic | EpCAM radionuclide molecular imaging SPECT iodine PIB |
| url | https://www.mdpi.com/1420-3049/25/20/4719 |
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