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|a 20210316d2020 k||y0rusy50 ba
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|a eng
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1 |
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|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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| 203 |
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|a Text
|c electronic
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| 320 |
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|a [References: 39 tit.]
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| 330 |
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|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 |
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|t International Journal of Molecular Sciences
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| 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 |
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|a radionuclide
|
| 610 |
1 |
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|a molecular imaging
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| 610 |
1 |
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|a SPECT
|
| 610 |
1 |
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|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
|
| 712 |
0 |
2 |
|a Национальный исследовательский Томский политехнический университет
|b Исследовательская школа химических и биомедицинских технологий
|b Научно-исследовательский центр "Онкотераностика"
|3 (RuTPU)RU\TPU\col\27561
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| 801 |
|
2 |
|a RU
|b 63413507
|c 20210316
|g RCR
|
| 850 |
|
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|a 63413507
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| 856 |
4 |
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|u https://doi.org/10.3390/ijms21093310
|
| 942 |
|
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|c CF
|