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Title: In Vitro Evaluation of a Specific Radiochemical Compound Based on 99mTc-labeled DARPinG3 for Radionuclide Imaging of Tumors Overexpressing Her-2/neu
Authors: Bragina, O.
Larkina, M.
Stasyuk (Stasiuk), Elena Sergeyevna
Chernov, Vladimir Ivanovich
Zelchan, Roman Vladimirovich
Medvedeva, Anna Aleksndrovna
Sinilkin, Ivan Gennadjevich
Yusubov, Mekhman Suleiman-Ogly (Suleimanovich)
Skuridin, Viktor Sergeyevich
Deev, Sergey Mikhaylovich
Buldakov, M.
Keywords: опухоли; диагностические методы; злокачественные опухоли; радиохимические соединения; выживаемость; визуализация; радиометрические исследования; радиофармацевтические препараты
Issue Date: 2017
Publisher: AIP Publishing
Citation: In Vitro Evaluation of a Specific Radiochemical Compound Based on 99mTc-labeled DARPinG3 for Radionuclide Imaging of Tumors Overexpressing Her-2/neu / O. Bragina [et al.] // AIP Conference Proceedings. — 2017. — Vol. 1882 : Physics of Cancer: Interdisciplinary Problems and Clinical Applications (PC IPCA’17) : Proceedings of the International conference, 23–26 May 2017, Tomsk, Russia. — [020007, 4 p.].
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 [mu]l (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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