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

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

Bibliographische Detailangaben
Parent link:International Journal of Molecular Sciences
Vol. 21, iss. 9.— 2020.— [3310, 13 p. ]
Körperschaft: Национальный исследовательский Томский политехнический университет Исследовательская школа химических и биомедицинских технологий Научно-исследовательский центр "Онкотераностика"
Weitere Verfasser: 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
Zusammenfassung: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.
Sprache:Englisch
Veröffentlicht: 2020
Schlagworte:
труды учёных ТПУ
электронный ресурс
EpCAM
radionuclide
molecular imaging
SPECT
iodine
PIB
ovarian
cancer
Online-Zugang:https://doi.org/10.3390/ijms21093310
Format: Elektronisch Buchkapitel
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=663887

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