Feasibility of imaging epcam expression in ovarian cancer using radiolabeled darpin ec1
Vorobyeva A., Konovalova E., Xu T., Schulga A., Altai M., Garousi J., Rinne S. S., Orlova A., Tolmachev V., Deev S. M.
International Journal of Molecular Sciences
Vol.21, Issue9, Num.3310
Опубликовано: 2020
Тип ресурса: Статья
Аннотация:
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 r
Ключевые слова:
Cancer; EpCAM; Iodine; Molecular imaging; Ovarian; PIB; Radionuclide; SPECT
4 iodobenzoic acid; epithelial cell adhesion molecule; iodine 125; ketamine; sodium metabisulfite; xylazine; animal experiment; animal model; animal tissue; antineoplastic activity; Article; binding affinity; BxPC-3 cell line; cell suspension; cell viability assay; controlled study; dissociation constant; drug distribution; female; human; human cell; isotope labeling; mouse; nonhuman; ovary cancer; OVCAR-3 cell line; radioactivity; radioiodination; Ramos cell line; single photon emission computed tomography-computed tomography; SK-OV-3-Luc cell line; thin layer chromatography; tissue distribution; tumor xenograft
Язык текста: Английский
ISSN: 1661-6596
Vorobyeva A.
Konovalova E.
Xu T.
Schulga A.
Altai M.
Garousi J.
Rinne S. S.
Orlova A.
Tolmachev V.
Deev S. M. Sergej Mikhaylovich 1951-
Воробьева А.
Коновалова Е.
Ху Т.
Счулга А.
Алтаи М.
Гароуси Й.
Ринне С. С.
Орлова А.
Толмачев В.
Деев С. М. Сергей Михайлович 1951-
Feasibility of imaging epcam expression in ovarian cancer using radiolabeled darpin ec1
Текст визуальный непосредственный
International Journal of Molecular Sciences
Vol.21, Issue9 Num.3310
2020
Статья
Cancer EpCAM Iodine Molecular imaging Ovarian PIB Radionuclide SPECT
4 iodobenzoic acid epithelial cell adhesion molecule iodine 125 ketamine sodium metabisulfite xylazine animal experiment animal model animal tissue antineoplastic activity Article binding affinity BxPC-3 cell line cell suspension cell viability assay controlled study dissociation constant drug distribution female human human cell isotope labeling mouse nonhuman ovary cancer OVCAR-3 cell line radioactivity radioiodination Ramos cell line single photon emission computed tomography-computed tomography SK-OV-3-Luc cell line thin layer chromatography tissue distribution tumor xenograft
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 r