Synthesis and Investigation of Radiopharmaceutical Complexes Based on 177Lu and 212Pb for the Targeted Therapy of Malignant Neoplasms

Abstract

The synthesis and investigation of a new bioconjugate for the targeted therapy of breast cancer is carried out. The ZHER2 scaffold polypeptide specific for the extracellular domain epitope of the HER2 transmembrane receptor, which is conjugated to a carrier molecule of human serum albumin (HSA) with the DOTA chelating agent attached to it, is used as the targeting agent. The radiolabeling reaction of the ZHER2–HSA–DOTA molecule is carried out with the 177Lu radionuclide, as well as with 212Pb, obtained using the developed laboratory generator. The radiochemical purity of the 177Lu-labeled preparation was 57 ± 10%, and that of the 212Pb-labeled preparation was 72 ± 5%. The degree of dissociative stability of these compounds was 73 ± 8% for 177Lu and more than 90% for 212Pb. In vitro tests of the cytotoxic activity of the obtained targeted radioactive compounds [177Lu]ZHER2–HSA–DOTA and [212Pb]ZHER2–HSA–DOTA in tumor-cell lines show a significant level of proliferation inhibition of the proliferation of human breast-cancer cells SK-BR-3 and BT474 with overexpression of the HER2/neu tumor marker in contrast to MCF-7 breast ductal adenocarcinoma cells with a low level of HER2/neu expression.