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

Результат исследований: Материалы для книги/типы отчетовМатериалы для конференции

Выдержка

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.

Язык оригиналаАнглийский
Название основной публикацииPhysics of Cancer
Подзаголовок основной публикацииInterdisciplinary Problems and Clinical Applications - Proceedings of the International Conference on Physics of Cancer: Interdisciplinary Problems and Clinical Applications, PC IPCA 2017
РедакторыElazar Y. Gutmanas, Oleg B. Naimark, Yurii P. Sharkeev
ИздательAmerican Institute of Physics Inc.
Том1882
ISBN (электронное издание)9780735415621
DOI
СостояниеОпубликовано - 28 сен 2017
СобытиеInternational Conference on Physics of Cancer: Interdisciplinary Problems and Clinical Applications, PC IPCA 2017 - Tomsk, Российская Федерация
Продолжительность: 23 мая 201726 мая 2017

Конференция

КонференцияInternational Conference on Physics of Cancer: Interdisciplinary Problems and Clinical Applications, PC IPCA 2017
СтранаРоссийская Федерация
ГородTomsk
Период23.5.1726.5.17

Отпечаток

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)

Цитировать

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. В E. Y. Gutmanas, O. B. Naimark, & Y. P. Sharkeev (Ред.), 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 (Том 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. ред. / Elazar Y. Gutmanas; Oleg B. Naimark; Yurii P. Sharkeev. Том 1882 American Institute of Physics Inc., 2017. 020007.

Результат исследований: Материалы для книги/типы отчетовМатериалы для конференции

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. в EY Gutmanas, OB Naimark & YP Sharkeev (ред.), 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. том. 1882, 020007, American Institute of Physics Inc., Tomsk, Российская Федерация, 23.5.17. https://doi.org/10.1063/1.5001586
Bragina O, Larkina M, Stasyuk E, Chernov V, Zelchan R, Medvedeva A и соавт. In vitro evaluation of a specific radiochemical compound based on 99mTc-labeled DARPinG3 for radionuclide imaging of tumors overexpressing Her-2/neu. В Gutmanas EY, Naimark OB, Sharkeev YP, редакторы, 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. Том 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. редактор / Elazar Y. Gutmanas ; Oleg B. Naimark ; Yurii P. Sharkeev. Том 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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AU - Larkina, M.

AU - Stasyuk, E.

AU - Chernov, V.

AU - Zelchan, R.

AU - Medvedeva, A.

AU - Sinilkin, I.

AU - Yusubov, M.

AU - Skuridin, V.

AU - Deyev, S.

AU - Buldakov, M.

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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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