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Article

Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1

1
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
2
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia
3
Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
4
Department of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, Sweden
5
Science for Life Laboratory, Uppsala University, 751 23 Uppsala, Sweden
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Bio-Nanophotonic Lab, Institute of Engineering Physics for Biomedicine (PhysBio), National Research Nuclear University ‘MEPhI’, 115409 Moscow, Russia
7
Center of Biomedical Engineering, Sechenov University, 119991 Moscow, Russia
*
Author to whom correspondence should be addressed.
A.V. and E.K. contributed equally.
Int. J. Mol. Sci. 2020, 21(9), 3310; https://doi.org/10.3390/ijms21093310
Received: 18 April 2020 / Revised: 3 May 2020 / Accepted: 5 May 2020 / Published: 7 May 2020
(This article belongs to the Special Issue Cancer Molecular Imaging)
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. View Full-Text
Keywords: EpCAM; radionuclide; molecular imaging; SPECT; iodine; PIB; ovarian; cancer EpCAM; radionuclide; molecular imaging; SPECT; iodine; PIB; ovarian; cancer
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MDPI and ACS Style

Vorobyeva, A.; Konovalova, E.; Xu, T.; Schulga, A.; Altai, M.; Garousi, J.; Rinne, S.S.; Orlova, A.; Tolmachev, V.; Deyev, S. Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1. Int. J. Mol. Sci. 2020, 21, 3310. https://doi.org/10.3390/ijms21093310

AMA Style

Vorobyeva A, Konovalova E, Xu T, Schulga A, Altai M, Garousi J, Rinne SS, Orlova A, Tolmachev V, Deyev S. Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1. International Journal of Molecular Sciences. 2020; 21(9):3310. https://doi.org/10.3390/ijms21093310

Chicago/Turabian Style

Vorobyeva, Anzhelika, Elena Konovalova, Tianqi Xu, Alexey Schulga, Mohamed Altai, Javad Garousi, Sara S. Rinne, Anna Orlova, Vladimir Tolmachev, and Sergey Deyev. 2020. "Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1" International Journal of Molecular Sciences 21, no. 9: 3310. https://doi.org/10.3390/ijms21093310

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