Publication: Radionuclide molecular imaging of EpCAM expression in triple-negative breast cancer using the scaffold protein DARPin Ec1
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2020
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© 2020 by the authors. Licensee MDPI, Basel, Switzerland.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.
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Radionuclide molecular imaging of EpCAM expression in triple-negative breast cancer using the scaffold protein DARPin Ec1 / Vorobyeva, A. [et al.] // Molecules. - 2020. - 25. - № 20. - 10.3390/molecules25204719
URI
https://www.doi.org/10.3390/molecules25204719
https://www.scopus.com/record/display.uri?eid=2-s2.0-85093651035&origin=resultslist
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000585559000001
https://openrepository.mephi.ru/handle/123456789/22505
https://www.scopus.com/record/display.uri?eid=2-s2.0-85093651035&origin=resultslist
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000585559000001
https://openrepository.mephi.ru/handle/123456789/22505