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Feasibility of Imag...
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Vorobyeva, AnzhelikaUppsala universitet,Medicinsk strålningsvetenskap,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
(author)
Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-05-07
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MDPI,2020
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electronicrdacarrier
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LIBRIS-ID:oai:DiVA.org:uu-413916
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-413916URI
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https://doi.org/10.3390/ijms21093310DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
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Konovalova, ElenaRussian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.
(author)
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Xu, TianqiUppsala universitet,Medicinsk strålningsvetenskap(Swepub:uu)tiaxu272
(author)
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Schulga, AlexeyTomsk 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.
(author)
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Altai, MohamedUppsala universitet,Medicinsk strålningsvetenskap(Swepub:uu)mohal988
(author)
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Garousi, JavadUppsala universitet,Medicinsk strålningsvetenskap(Swepub:uu)javga723
(author)
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Rinne, Sara S.Uppsala universitet,Theranostics(Swepub:uu)sarri895
(author)
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Orlova, Anna,1960-Uppsala universitet,Theranostics,Science for Life Laboratory, SciLifeLab,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia(Swepub:uu)annaorlo
(author)
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Tolmachev, VladimirUppsala universitet,Medicinsk strålningsvetenskap,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.(Swepub:uu)vladtolm
(author)
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Deyev, SergeyTomsk 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.
(author)
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Uppsala universitetMedicinsk strålningsvetenskap
(creator_code:org_t)
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In:International Journal of Molecular Sciences: MDPI21:91661-65961422-0067
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