RESUMO
Two radiopharmaceutical preparations were developed on the basis of artificial targeted polypeptide ZHER2 specific to HER2/neu tumor marker and radionuclides 177Lu (ZHER2-HSA-chelator-177Lu) or 212Pb (ZHER2-HSA-chelator-212Pb). The objective was to evaluate in vitro the cytotoxic activity of the targeted radiopharmaceuticals using two cultured human breast cancer cell lines with different expression of HER2/neu: SK-BR3 (high expression of HER2/neu) and MCF-7 (low expression of HER2/neu). It was shown that the cytotoxic effect of both preparations was significantly higher against the SK-BR-3 cells. The cytotoxicity correlated with the incubation period (it was higher after 72 h than after 24 h) and was significantly more pronounced in comparison with activity of radionuclide salts without a specific ligand. In vivo preclinical study of these pharmaceuticals seems to be very promising in animals with xenografted tumors showing high expression of HER2/neu marker.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/radioterapia , Imunotoxinas/uso terapêutico , Radioisótopos de Chumbo/uso terapêutico , Lutécio/uso terapêutico , Radioisótopos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Radioisótopos de Chumbo/química , Células MCF-7 , Terapia de Alvo Molecular/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Especificidade por SubstratoRESUMO
The new method for medical (89)Sr production in a reactor with solution fuel is proposed which is characterized by simplicity, high production efficiency and low buildup of radioactive waste. The main advantages of the new technology were validated by numerous experiments. The proposed new technology selectively extracts (89)Sr from a fuel of solution reactor and precludes penetration of (90)Sr into the final product. This method is based on the presence of gaseous radionuclide (89)Kr (T(1/2)=190.7s) in the decay chain (89)Se-->(89)Br-->(89)Kr-->(89)Rb-->(89)Sr. The performed experiments on taking the gas probes from internal volume of the solution 20 kW mini-reactor "Argus" have confirmed that the mechanism for (89)Sr delivery to the sorption volume of the reactor experimental loop is based on transport of gaseous (89)Sr predecessor-radionuclide (89)Kr. According to the measurements of radioactive impurities in a final (89)SrCl(2) solution, the filtration of the gas flow with cermet filters followed by cleaning of (89)Sr chloride solution in chromatographic columns with DOWEX-50 x 8 or Sr-Resin ensures reception of (89)Sr fully meeting the requirements for medical application. The experimental estimations have shown that the proposed new technology is multiply more productive than the traditional industrial methods of (89)Sr reception.