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

Bioorg Med Chem

Instituto de Pesquisas Energéticas e Nucleares/Comissão Nacional de Energia Nuclear (IPEN-CNEN), Avenida Professor Lineu Prestes, 2242, Sao Paulo 05508-000, Brazil.

Published: March 2021

AI Article Synopsis

  • The study assessed two radioimmunoconjugates, In-DTPA-trastuzumab and Lu-DOTA-trastuzumab, focusing on how different chelating agents affect their properties and binding to HER2 tumor cells.
  • Despite the variations in chelating agents, the molar ratios (1:10 and 1:20) did not compromise the integrity, labeling process, or stability of the antibodies.
  • However, notable differences were found in the lipophilicity and binding efficiency to HER2 positive SK-BR-3 cells, indicating that selecting the right chelating agent and ratio is crucial for developing effective radioimmunoconjugates.

Article Abstract

In the present work, the radioimmunoconjugates In-DTPA-trastuzumab and Lu-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.

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Source
http://dx.doi.org/10.1016/j.bmc.2021.115996DOI Listing

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