Specific Cytotoxicity of Targeted 177Lu and 212Pb-Based Radiopharmaceuticals

Bull Exp Biol Med. 2021 Sep;171(5):627-632. doi: 10.1007/s10517-021-05283-4. Epub 2021 Oct 9.

Abstract

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.

Keywords: 177Lu and 212Pb radionuclides; targeted radiopharmaceutical.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunotoxins / therapeutic use*
  • Lead Radioisotopes / chemistry
  • Lead Radioisotopes / therapeutic use*
  • Lutetium / therapeutic use*
  • MCF-7 Cells
  • Molecular Targeted Therapy / methods
  • Radioisotopes / therapeutic use*
  • Radiopharmaceuticals / therapeutic use
  • Substrate Specificity

Substances

  • Antineoplastic Agents
  • Immunotoxins
  • Lead Radioisotopes
  • Radioisotopes
  • Radiopharmaceuticals
  • Lutetium
  • Lutetium-177