Anti-HER2 monoclonal antibody based-radioimmunoconjugates: Assessment of the chelating agent influence

Bioorg Med Chem. 2021 Mar 1:33:115996. doi: 10.1016/j.bmc.2021.115996. Epub 2021 Jan 10.

Abstract

In the present work, the radioimmunoconjugates 111In-DTPA-trastuzumab and 177Lu-DOTA-trastuzumab were evaluated regarding the influence of the chelating agents on the physical-chemical parameters and human epidermal growth factor receptor 2 (HER2) tumor cell binding. Data showed that both chelating agents, at predetermined molar ratios (antibody:chelator - 1:10 and 1:20), did not influence the immunoconjugates integrity, the radiolabeling process and the radiolabeled antibodies stability. However, differences were observed in the lipophilic feature between DOTA and DTPA radioimmunoconjugates and in the specific binding to SK-BR-3 tumor cells (HER2 positive). Therefore, this study showed the importance of assessing the influence of chelating agents and their molar ratios in the development process of radioimmunoconjugates.

Keywords: (111)In-DTPA-trastuzumab; (177)Lu-DOTA-trastuzumab; Antibody:chelator molar ratio; Radioimmunoconjugate; Trastuzumab.

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology*
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacology*
  • Molecular Structure
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Chelating Agents
  • Immunoconjugates
  • ERBB2 protein, human
  • Receptor, ErbB-2