May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Ocular Tissue Distribution of a Full–Length Antibody and an Antibody Fab Fragment to Vascular Endothelial Growth Factor After Intravitreal Administration in the Rabbit
Author Affiliations & Notes
  • L.A. Damico
    Genentech Inc, South San Francisco, CA
    Pharmacokinetic & Pharmacodynamic Sciences,
  • P.C. Haughney
    Genentech Inc, South San Francisco, CA
    Pharmacokinetic & Pharmacodynamic Sciences,
  • L.T. Berleau
    Genentech Inc, South San Francisco, CA
    Regulatory Affairs,
  • J.C. Beyer
    Genentech Inc, South San Francisco, CA
    Safety Assessment,
  • Footnotes
    Commercial Relationships  L.A. Damico, Genentech, Inc., I; Genentech, Inc, E; P.C. Haughney, Genentech, Inc., I; Genentech, Inc, E; L.T. Berleau, Genentech, Inc., I; Genentech, Inc, E; J.C. Beyer, Genentech, Inc., I; Genentech, Inc, E.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 3887. doi:
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      L.A. Damico, P.C. Haughney, L.T. Berleau, J.C. Beyer; Ocular Tissue Distribution of a Full–Length Antibody and an Antibody Fab Fragment to Vascular Endothelial Growth Factor After Intravitreal Administration in the Rabbit . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3887.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To assess the ocular tissue distribution of full–length anti–VEGF monoclonal antibody A.4.6.1 and anti–VEGF Fab chimera after intravitreal administration in New Zeeland White Rabbits. A.4.6.1 is a murine monoclonal antibody to human vascular endothelial growth factor (VEGF). The chimeric Fab is a molecule generated by grafting the variable heavy and variable light domains of A.4.6.1 onto the human Constant Heavy 1 and Constant Light domains.

Methods: : 125I–labeled A.4.6.1 and 125I–labeled anti–VEGF Fab chimera (8µCi/eye and 25 µg total protein/eye, 50 µL per injection) were administered by bilateral intravitreal injection to 5 rabbits per group. One animal from each group was sacrificed at 1 hour, 24 hours, 4 days, 7 days and 14 days after dosing. At sacrifice, both globes were injected with 100 µL of 20% formalin followed by immersion fixation in 10% neutral buffered formalin and routine processing for microradiography. The distribution of radiolabeled material in each eye was evaluated.

Results: : The anti–VEGF Fab chimera moved rapidly from the inner nuclear layer at 1 hour to the photoreceoptor layer at 24 hours, where it persisted without further movement on Day 7 and was a background levels on Day 14. The intact anti–VEGF antibody had slower movement across the retina, reaching the inner limiting membrane by 1 hour and the external plexiform layer by Day 4, where it remained until Day 14.

Conclusions: : The observed penetration of 125I–labeled proteins across the retina was related to the size of the molecule with the anti–VEGF Fab chimera reaching the photoreceptor layer and the full–length antibody penetrating to the external plexiform layer.

Keywords: retina • anatomy • growth factors/growth factor receptors 
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