title: Penetration of bevacizumab through the retina after intravitreal injection in the monkey.
abstract: OBJECTIVE
  The penetration of intravitreally injected bevacizumab in its commercial formulation (Avastin; Roche, Grenzach, Germany) through the retina was studied, to determine whether a full-length antibody would be able to penetrate the retina as easily as an antibody fragment.
  
  
  METHODS
  Six cynomolgus monkeys (Macaca fascicularis) were used in this study. Two compositions of intravitreal injection into the right eyes were performed: one with commercial Avastin (group 1, four animals) and the other one with commercial Avastin labeled with 125I (group 2, one animal). The animals in group 1 were killed 1, 4, 7, or 14 days after the injection for subsequent histologic analysis of the eyes by immunohistochemistry, and the animal in group 2 was killed 7 days after injection for autoradiography and electron microscopy. Funduscopy was performed before the injection and at several time points thereafter. Moreover, blood samples were collected at different time points from the group-2 animal. The sixth animal remained untreated and served as the control.
  
  
  RESULTS
  No pathologic changes were obvious in the funduscopic images within the time of the experiment. Bevacizumab immunoreactivity was found in the choroid and the inner layers of the retina as early as 1 day after the injection and spread to the outer layers and the choroid within the following days, in particular to photoreceptors and blood vessels. Avastin labeled with 125I showed radioactivity in blood serum 1 day after the intravitreal injection and remained relatively stable until day 7.
  
  
  CONCLUSIONS
  The results clearly show that the bevacizumab molecule can penetrate the retina and is also transported into the retinal pigment epithelium, the choroid and, in particular, into photoreceptor outer segments after intravitreal injection of Avastin. Active transport mechanisms seem to be involved.
authors.affiliation: Experimental Vitreoretinal Surgery, Germany. p.heiduschka@uni-tuebingen.de
authors.forename: Peter
authors.initials: P
authors.lastname: Heiduschka
authors.forename: Heike
authors.initials: H
authors.lastname: Fietz
authors.forename: Sabine
authors.initials: S
authors.lastname: Hofmeister
authors.forename: Sigrid
authors.initials: S
authors.lastname: Schultheiss
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Mack
authors.forename: Swaantje
authors.initials: S
authors.lastname: Peters
authors.forename: Focke
authors.initials: F
authors.lastname: Ziemssen
authors.forename: Birgit
authors.initials: B
authors.lastname: Niggemann
authors.forename: Sylvie
authors.initials: S
authors.lastname: Julien
authors.forename: Karl Ulrich
authors.initials: KU
authors.lastname: Bartz-Schmidt
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schraermeyer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D001345:Autoradiography; D000068258:Bevacizumab; D001692:Biological Transport; D002829:Choroid / Q000378:metabolism / Q000648:ultrastructure; D019084:Fluorescent Antibody Technique, Indirect; D007267:Injections; D008252:Macaca fascicularis; D010781:Photography; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000648:ultrastructure; D012160:Retina / Q000378:metabolism* / Q000648:ultrastructure; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014822:Vitreous Body
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab