Publication:
Feasibility of imaging epcam expression in ovarian cancer using radiolabeled darpin ec1

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W3023746890.pdf(2.12 MB)
Дата
2020
Авторы
Vorobyeva, A.
Konovalova, E.
Xu, T.
Schulga, A.
Deyev, S.
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Научные группы
Организационные подразделения
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Организационная единица
Инженерно-физический институт биомедицины
Цель ИФИБ и стратегия развития – это подготовка высококвалифицированных кадров на базе передовых исследований и разработок новых перспективных методов и материалов в области инженерно-физической биомедицины. Занятие лидерских позиций в биомедицинских технологиях XXI века и внедрение их в образовательный процесс, что отвечает решению практикоориентированной задачи мирового уровня – диагностике и терапии на клеточном уровне социально-значимых заболеваний человека.
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Аннотация
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.Epithelial cell adhesion molecule (EpCAM) is overexpressed in 55%–75% of ovarian carcinomas (OC). EpCAM might be used as a target for a treatment of disseminated OC. Designed ankyrin repeats protein (DARPin) Ec1 is a small (18 kDa) protein, which binds to EpCAM with subnanomolar affinity. We tested a hypothesis that Ec1 labeled with a non-residualizing label might serve as a companion imaging diagnostic for stratification of patients for EpCAM-targeting therapy. Ec1 was labeled with125I using N-succinimidyl-para-iodobenzoate. Binding affinity, specificity, and cellular processing of [125 I]I-PIB-Ec1 were evaluated using SKOV-3 and OVCAR-3 ovarian carcinoma cell lines. Biodistribution and tumor-targeting properties of [125 I]I-PIB-Ec1 were studied in Balb/c nu/nu mice bearing SKOV-3 and OVCAR-3 xenografts. EpCAM-negative Ramos lymphoma xenografts served as specificity control. Binding of [125 I]I-PIB-Ec1 to ovarian carcinoma cell lines was highly specific and had affinity in picomolar range. Slow internalization of [125 I]I-PIB-Ec1 by OC cells confirmed utility of non-residualizing label for in vivo imaging. [125I]I-PIB-Ec1 provided 6 h after injection tumor-to-blood ratios of 30 ± 11 and 48 ± 12 for OVCAR-3 and SKOV-3 xenografts, respectively, and high contrast to other organs. Tumor targeting was highly specific. Saturation of tumor uptake at a high dose of Ec1 in SKOV-3 model provided a rationale for dose selection in further studies using therapeutic conjugates of Ec1 for targeted therapy. In conclusion, [125I]I-PIB-Ec1 is a promising agent for visualizing EpCAM expression in OC.
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Feasibility of imaging epcam expression in ovarian cancer using radiolabeled darpin ec1 / Vorobyeva, A. [et al.] // International Journal of Molecular Sciences. - 2020. - 21. - № 9. - 10.3390/ijms21093310
URI
https://www.doi.org/10.3390/ijms21093310
 https://www.scopus.com/record/display.uri?eid=2-s2.0-85084269592&origin=resultslist
 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000535581700281
 https://openrepository.mephi.ru/handle/123456789/21639
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