Pharmacokinetics and Biodistribution Study of 7A7 Anti-Mouse Epidermal Growth Factor Receptor Monoclonal Antibody and Its F(ab’)2 Fragment in an Immunocompetent Mouse Model

• Published in: ISRN pharmacology Vol. 2012; no. 2012; pp. 1 - 8
• Main Authors: Rabasa Capote, Ailem, González, Jorge Ernesto, Rodríguez-Vera, Leyanis, López, Armando, Sánchez Ramírez, Belinda, Garrido Hidalgo, Greta
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2012; International Scholarly Research Network; Hindawi Limited
• Subjects: Animal models; Antitumor activity; Cloning; Data processing; Enzyme-linked immunosorbent assay; Epidermal growth factor receptors; Fc receptors; Growth factor receptors; Kidney; Laboratory animals; Liver; Lung; Lungs; Molecular modelling; Monoclonal antibodies; Pharmacokinetics; Signal transduction; Spleen; Studies; Tumors
• ISSN: 2090-5165; 2090-5173
• DOI: 10.5402/2012/417515

Immunocompetent mice, Fc receptor γ-chain deficient mice (Fcer1g−/−), and molecular tools as F(ab′)2 bivalent fragments appear as the most suitable biological models to study the mechanisms of the action of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs). In vivo experiments contrasting antitumor effects of whole Abs and their bivalent fragments commonly involve a previous comparative pharmacokinetics study. In this paper, pharmacokinetics and biodistribution of an anti-mouse EGFR Ab were assessed using immunocompetent mice. 125I-labeled 7A7 mAb holds an elimination half-life (t1/2β) of 23.1 h in C57BL/6 mice. Accumulation of mAb was found in liver, spleen, kidneys, and mostly in lungs. We used an ELISA method to determine the t1/2β of a 7A7 mAb using the same experimental setting. Results from this new analysis revealed a t1/2β of 23.9 h, supporting this method as a safer and easier system to evaluate pharmacokinetics parameters of mAbs targeting mouse EGFR. Using this system we also studied pharmacokinetics of 7A7 F(ab′)2 fragment. A tenfold difference between the mAb and fragment t1/2β was found. These data support the use of the 7A7 F(ab′)2 fragment in in vivo studies to explore the contribution of the EGFR signaling blockade and the Fc region to the antitumor effect of 7A7 mAb in this autologous scenario.