Specific Cytotoxicity of Targeted [sup.177]Lu and [sup.212]Pb-Based Radiopharmaceuticals

• Published in: Bulletin of experimental biology and medicine 2021-09, Vol.171 (5), p.627
• Main Authors: Pankratov, A.A, Nemtsova, E.R, Plyutinskaya, A.D, Vorontsova, M.S, Chuvilin, D.Yu, Egorova, B.V, Kokov, K.V, Deev, S.M, Lebedenko, E.N, Proshkina, G.M, Shul'ga, A.A, Golovachenko, V.A, Shegai, P.V, Kaprin, A.D
• Format: Article
• Language: English
• ISSN: 0007-4888
• DOI: 10.1007/s10517-021-05283-4

Two radiopharmaceutical preparations were developed on the basis of artificial targeted polypeptide ZHER2 specific to HER2/neu tumor marker and radionuclides [sup.177]Lu (ZHER2-HSA-chelator-[sup.177]Lu) or [sup.212]Pb (ZHER2-HSA-chelator-[sup.212]Pb). 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. Key Words: targeted radiopharmaceutical; [sup.177]Lu and [sup.212]Pb radionuclides