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

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cultured cells
radioactive isotopes
tumors
breast
evaluation
cells
phosphates
trypsin
ethylenediaminetetraacetic acids
washing
albumins
chutes
serums
purity
buffers
chambers
cancer
tubes
output

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Cite this

Bragina, O., Larkina, M., Stasyuk, E., Chernov, V., Zelchan, R., Medvedeva, A., ... 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

In vitro evaluation of a specific radiochemical compound based on 99mTc-labeled DARPinG3 for radionuclide imaging of tumors overexpressing Her-2/neu. / Bragina, O.; Larkina, M.; Stasyuk, E.; Chernov, V.; Zelchan, R.; Medvedeva, A.; Sinilkin, I.; Yusubov, M.; Skuridin, V.; Deyev, S.; Buldakov, M.

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. ed. / Elazar Y. Gutmanas; Oleg B. Naimark; Yurii P. Sharkeev. Vol. 1882 American Institute of Physics Inc., 2017. 020007.

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

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 EY Gutmanas, OB Naimark & YP 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., International Conference on Physics of Cancer: Interdisciplinary Problems and Clinical Applications, PC IPCA 2017, Tomsk, Russian Federation, 23.5.17. https://doi.org/10.1063/1.5001586
Bragina O, Larkina M, Stasyuk E, Chernov V, Zelchan R, Medvedeva A et al. In vitro evaluation of a specific radiochemical compound based on 99mTc-labeled DARPinG3 for radionuclide imaging of tumors overexpressing Her-2/neu. In Gutmanas EY, Naimark OB, Sharkeev YP, editors, 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. American Institute of Physics Inc. 2017. 020007 https://doi.org/10.1063/1.5001586
Bragina, O. ; Larkina, M. ; Stasyuk, E. ; Chernov, V. ; Zelchan, R. ; Medvedeva, A. ; Sinilkin, I. ; Yusubov, M. ; Skuridin, V. ; Deyev, S. ; Buldakov, M. / In vitro evaluation of a specific radiochemical compound based on 99mTc-labeled DARPinG3 for radionuclide imaging of tumors overexpressing Her-2/neu. 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. editor / Elazar Y. Gutmanas ; Oleg B. Naimark ; Yurii P. Sharkeev. Vol. 1882 American Institute of Physics Inc., 2017.
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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.",
author = "O. Bragina and M. Larkina and E. Stasyuk and V. Chernov and R. Zelchan and A. Medvedeva and I. Sinilkin and M. Yusubov and V. Skuridin and S. Deyev and M. Buldakov",
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N2 - 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.

AB - 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.

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