In vitro evaluation of a specific radiochemical compound based on 99mTc-labeled DARPinG3 for radionuclide imaging of tumors overexpressing Her-2/neu

O. Bragina, M. Larkina, E. Stasyuk, V. Chernov, R. Zelchan, A. Medvedeva, I. Sinilkin, M. Yusubov, V. Skuridin, S. Deyev, M. Buldakov

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

It is still necessary to search for new informative diagnostic methods to detect malignant tumors with overexpression of Her-2/neu, which are characterized by the aggressive course of the disease, rapid rate of tumor growth and low rates of relapse-free and overall survival. In recent years, the radioisotope techniques for detection of specific tumor targets have been developing actively. Purpose: to develop a chemically stable radiochemical compound for the targeted imaging of cells overexpressing Her-2/neu. Material and methods: The study was performed using 2 cell lines. The human breast adenocarcinoma HER2-overexpressing cell line BT-474 was chosen to detect specific binding. As a control, HER2-negative human breast adenocarcinoma MCF-7 was used. The human breast adenocarcinoma BT-474 and MCF-7 cell lines were seeded in chamber-slides at the density of 35,000 cells/ml in trypsin-EDTA (PanEco) medium and grown overnight at 37°C. After that both cell lines were washed with Phosphate buffered saline (PBS) and distributed into test tubes to 1 ml (5 millions cells in each). After adding 100 μl (70 MBq) studied complex of 99mTc-DPAH- DARPinG3 was incubated for 40 min at +4°C. Washing was performed three times with buffer PBS and 5% Bovine Serum Albumin (BSA). The characteristics of the binding specificity of the test set with the HER-2/neu receptor were determined by direct radiometric and planar scintigraphy. Nonparametric Mann-Whitney test was used to assess the differences in the quantitative characteristics between groups. Results: The output of the labeled complex was more than 91%, with a radiochemical purity of more than 94%. When carrying out a visual scintigraphic assessment much greater intensity accumulation of radiotracer was observed in the studied cell culture surface receptor overexpressing Her-2/neu. The results of direct radiometric also showed higher accumulation of the radiopharmaceutical in the adenocarcinoma cell line BT-474 human breast cancer overexpressing Her-2/neu compared to the control group. Conclusion: The preclinical studies demonstrated a high in vitro stability of the study compound, as well as its accumulation in the cell group overexpressing Her-2/neu.

Original languageEnglish
Title of host publicationPhysics of Cancer
Subtitle of host publicationInterdisciplinary Problems and Clinical Applications - Proceedings of the International Conference on Physics of Cancer: Interdisciplinary Problems and Clinical Applications, PC IPCA 2017
EditorsElazar Y. Gutmanas, Oleg B. Naimark, Yurii P. Sharkeev
PublisherAmerican Institute of Physics Inc.
Volume1882
ISBN (Electronic)9780735415621
DOIs
Publication statusPublished - 28 Sep 2017
EventInternational Conference on Physics of Cancer: Interdisciplinary Problems and Clinical Applications, PC IPCA 2017 - Tomsk, Russian Federation
Duration: 23 May 201726 May 2017

Conference

ConferenceInternational Conference on Physics of Cancer: Interdisciplinary Problems and Clinical Applications, PC IPCA 2017
CountryRussian Federation
CityTomsk
Period23.5.1726.5.17

ASJC Scopus subject areas

  • Physics and Astronomy(all)

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    Bragina, O., Larkina, M., Stasyuk, E., Chernov, V., Zelchan, R., Medvedeva, A., Sinilkin, I., Yusubov, M., Skuridin, V., Deyev, S., & Buldakov, M. (2017). In vitro evaluation of a specific radiochemical compound based on 99mTc-labeled DARPinG3 for radionuclide imaging of tumors overexpressing Her-2/neu. In E. Y. Gutmanas, O. B. Naimark, & Y. P. Sharkeev (Eds.), Physics of Cancer: Interdisciplinary Problems and Clinical Applications - Proceedings of the International Conference on Physics of Cancer: Interdisciplinary Problems and Clinical Applications, PC IPCA 2017 (Vol. 1882). [020007] American Institute of Physics Inc.. https://doi.org/10.1063/1.5001586