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Feasibility of Imag...
Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1
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- Vorobyeva, Anzhelika (author)
- Uppsala universitet,Medicinsk strålningsvetenskap,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
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- Konovalova, Elena (author)
- Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.
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- Xu, Tianqi (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Schulga, Alexey (author)
- Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.;Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.
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- Altai, Mohamed (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Garousi, Javad (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Rinne, Sara S. (author)
- Uppsala universitet,Theranostics
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- Orlova, Anna, 1960- (author)
- Uppsala universitet,Theranostics,Science for Life Laboratory, SciLifeLab,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Medicinsk strålningsvetenskap,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
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- Deyev, Sergey (author)
- Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.;Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.;Natl Res Nucl Univ MEPhI, Inst Engn Phys Biomed PhysBio, Bionanophoton Lab, Moscow 115409, Russia.;Sechenov Univ, Ctr Biomed Engn, Moscow 119991, Russia.
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(creator_code:org_t)
- 2020-05-07
- 2020
- English.
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In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:9
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Abstract
Subject headings
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- 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 I-125 using N-succinimidyl-para-iodobenzoate. Binding affinity, specificity, and cellular processing of [I-125]I-PIB-Ec1 were evaluated using SKOV-3 and OVCAR-3 ovarian carcinoma cell lines. Biodistribution and tumor-targeting properties of [I-125]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 [I-125]I-PIB-Ec1 to ovarian carcinoma cell lines was highly specific and had affinity in picomolar range. Slow internalization of [I-125]I-PIB-Ec1 by OC cells confirmed utility of non-residualizing label for in vivo imaging. [I-125]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, [I-125]I-PIB-Ec1 is a promising agent for visualizing EpCAM expression in OC.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Keyword
- EpCAM
- radionuclide
- molecular imaging
- SPECT
- iodine
- PIB
- ovarian
- cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Vorobyeva, Anzhe ...
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Konovalova, Elen ...
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Xu, Tianqi
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Schulga, Alexey
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Altai, Mohamed
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Garousi, Javad
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Rinne, Sara S.
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Orlova, Anna, 19 ...
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Tolmachev, Vladi ...
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Deyev, Sergey
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Radiology Nuclea ...
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Uppsala University