Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1; International Journal of Molecular Sciences; Vol. 21, iss. 9

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Parent link:International Journal of Molecular Sciences
Vol. 21, iss. 9.— 2020.— [3310, 13 p. ]
Tác giả của công ty: Национальный исследовательский Томский политехнический университет Исследовательская школа химических и биомедицинских технологий Научно-исследовательский центр "Онкотераностика"
Tác giả khác: Vorobjeva (Vorobyeva) A. G. Anzhelika Grigorjevna, Konovalova E. V. Elena Valerjevna, Xu Tianqi, Shulga (Schulga) A. A. Aleksey Anatolievich, Altai M. Mohamed, Garousi J. Javad, Rinne S. S. Sara, Orlova A. M. Anna Markovna, Tolmachev V. M. Vladimir Maksimilianovich, Deev S. M. Sergey Mikhaylovich
Tóm tắt: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 with 125I using N-succinimidyl-para-iodobenzoate. Binding affinity, specificity, and cellular processing of [125I]I-PIB-Ec1 were evaluated using SKOV-3 and OVCAR-3 ovarian carcinoma cell lines. Biodistribution and tumor-targeting properties of [125I]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 [125I]I-PIB-Ec1 to ovarian carcinoma cell lines was highly specific and had affinity in picomolar range. Slow internalization of [125I]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.
Ngôn ngữ:Tiếng Anh
Được phát hành: 2020
Những chủ đề:
Truy cập trực tuyến:https://doi.org/10.3390/ijms21093310
Định dạng: Điện tử Chương của sách
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=663887

MARC

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200 1 |a Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1  |f A. G. Vorobjeva (Vorobyeva), E. V. Konovalova, Xu Tianqi [et al.] 
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330 |a 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 with 125I using N-succinimidyl-para-iodobenzoate. Binding affinity, specificity, and cellular processing of [125I]I-PIB-Ec1 were evaluated using SKOV-3 and OVCAR-3 ovarian carcinoma cell lines. Biodistribution and tumor-targeting properties of [125I]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 [125I]I-PIB-Ec1 to ovarian carcinoma cell lines was highly specific and had affinity in picomolar range. Slow internalization of [125I]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. 
461 |t International Journal of Molecular Sciences 
463 |t Vol. 21, iss. 9  |v [3310, 13 p. ]  |d 2020 
610 1 |a труды учёных ТПУ 
610 1 |a электронный ресурс 
610 1 |a EpCAM 
610 1 |a radionuclide 
610 1 |a molecular imaging 
610 1 |a SPECT 
610 1 |a iodine 
610 1 |a PIB 
610 1 |a ovarian 
610 1 |a cancer 
701 1 |a Vorobjeva (Vorobyeva)  |b A. G.  |c specialist in the field of medical technology  |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D  |f 1990-  |g Anzhelika Grigorjevna  |3 (RuTPU)RU\TPU\pers\46556  |9 22214 
701 1 |a Konovalova  |b E. V.  |c specialist in the field of chemical technology and biotechnology  |c engineer at Tomsk Polytechnic University  |f 1985-  |g Elena Valerjevna  |9 88562 
701 0 |a Xu Tianqi 
701 1 |a Shulga (Schulga)  |b A. A.  |c biologist  |c Researcher, Tomsk Polytechnic University, Candidate of Biological Sciences  |f 1960-  |g Aleksey Anatolievich  |3 (RuTPU)RU\TPU\pers\46796  |9 22432 
701 1 |a Altai  |b M.  |g Mohamed 
701 1 |a Garousi  |b J.  |g Javad 
701 1 |a Rinne  |b S. S.  |g Sara 
701 1 |a Orlova  |b A. M.  |c specialist in the field of medical technology  |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D  |f 1960-  |g Anna Markovna  |3 (RuTPU)RU\TPU\pers\46554  |9 22212 
701 1 |a Tolmachev  |b V. M.  |c specialist in the field of medical technology  |c Director of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D  |f 1961-  |g Vladimir Maksimilianovich  |3 (RuTPU)RU\TPU\pers\46552  |9 22210 
701 1 |a Deev  |b S. M.  |c biologist  |c Leading Researcher, Tomsk Polytechnic University, Doctor of Biological Sciences  |f 1951-  |g Sergey Mikhaylovich  |3 (RuTPU)RU\TPU\pers\39299  |9 20959 
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