Effect of a radiolabel biochemical nature on tumor-targeting properties of EpCAM-binding engineered scaffold protein DARPin Ec1; International Journal of Biological Macromolecules; Vol. 145

Effect of a radiolabel biochemical nature on tumor-targeting properties of EpCAM-binding engineered scaffold protein DARPin Ec1; International Journal of Biological Macromolecules; Vol. 145

Detalles Bibliográficos
Parent link:International Journal of Biological Macromolecules
Vol. 145.— 2020.— [P. 216-225]
Autor Corporativo: Национальный исследовательский Томский политехнический университет Исследовательская школа химических и биомедицинских технологий Научно-исследовательский центр "Онкотераностика"
Outros autores: Deev S. M. Sergey Mikhaylovich, Vorobjeva (Vorobyeva) A. G. Anzhelika Grigorjevna, Shulga (Schulga) A. A. Aleksey Anatolievich, Abouzayed A. Ayman, Gunther T. Tyran, Garousi J. Javad, Konovalova E. V. Elena Valerjevna, Ding H., Graslund T., Orlova A. M. Anna Markovna, Tolmachev V. M. Vladimir Maksimilianovich
Summary:Title screen
Radionuclide-based imaging of molecular therapeutic targets might facilitate stratifying patients for specific biotherapeutics. New type of imaging probes, based on designed ankyrin repeat proteins (DARPins), have demonstrated excellent contrast of imaging of human epidermal growth factor type 2 (HER2) expression in preclinical models. We hypothesized that labeling approaches, which result in lipophilic radiometabolites (non-residualizing labels), would provide the best imaging contrast for DARPins that internalize slowly after binding to cancer cells. The hypothesis was tested using DARPin Ec1 that binds to epithelial cell adhesion molecule (EpCAM). EpCAM is a promising therapeutic target. Ec1 was labeled with 125I using two methods to obtain the non-residualizing labels, while residualizing labels were obtained by labeling it with 99mTc. All labeled Ec1 variants preserved target specificity and picomolar binding affinity to EpCAM-expressing pancreatic adenocarcinoma BxPC-3 cells. In murine models, all the variants provided similar tumor uptake. However, 125I-PIB-H6-Ec1 had noticeably lower retention in normal tissues, which provided appreciably higher tumor-to-organ ratios. Furthermore, 125I-PIB-H6-Ec1 demonstrated the highest imaging contrast in preclinical models than any other EpCAM-imaging agent tested so far. In conclusion, DARPin Ec1 in combination with a non-residualizing label is a promising probe for imaging EpCAM expression a few hours after injection.
Режим доступа: по договору с организацией-держателем ресурса
Idioma:inglés
Publicado: 2020
Subjects:
электронный ресурс
труды учёных ТПУ
designed ankyrin repeat protein
EpCAM
labeling
structure-property relationship
biodistribution
Acceso en liña:https://doi.org/10.1016/j.ijbiomac.2019.12.147
Formato: Electrónico Capítulo de libro
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=664032

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