Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1; Molecules; Vol. 25, iss. 20
| Parent link: | Molecules Vol. 25, iss. 20.— 2020.— [4719, 20 p.] |
|---|---|
| Corporate Authors: | Национальный исследовательский Томский политехнический университет Исследовательская школа химических и биомедицинских технологий, Национальный исследовательский Томский политехнический университет Исследовательская школа химических и биомедицинских технологий Научно-исследовательский центр "Онкотераностика" |
| Other Authors: | Vorobjeva (Vorobyeva) A. G. Anzhelika Grigorjevna, Bezverkhniaia E. A. Ekaterina Aleksandrovna, Konovalova E. V. Elena Valerjevna, Shulga (Schulga) A. A. Aleksey Anatolievich, Garousi Ja. Javad, Vorontsova O. Olga, Abouzayed A. Ayman, Orlova A. M. Anna Markovna, Deev S. M. Sergey Mikhaylovich, Tolmachev V. M. Vladimir Maksimilianovich |
| Summary: | Title screen 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. |
| Language: | English |
| Published: |
2020
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| Subjects: | |
| Online Access: | https://doi.org/10.3390/molecules25204719 |
| Format: | Electronic Book Chapter |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=664643 |
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