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

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.

• Authors: Ana Cláudia Camargo Miranda, Ana Claudia Ranucci Durante, Leonardo Lima Fuscaldi, Angélica Bueno Barbezan, Cilene Rebouças de Lima, Efrain Perini, Elaine Bortoleti de Araújo
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 33 Pg. 115996 (03 01 2021) ISSN: 1464-3391 [Electronic] England
• PMID: 33494011 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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