Pharmacokinetics and blood-brain barrier transport of an anti-transferrin receptor monoclonal antibody (OX26) in rats after chronic treatment with the antibody.
Monoclonal antibodies (MAbs) directed against cell surface receptors (e.g. the transferrin receptor or the insulin receptor) on the brain capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo, are brain drug-delivery vectors. When cells are chronically exposed to MAbs in tissue culture, there is often down-regulation of the cell surface receptors. To examine whether similar down-regulation occurs in vivo, rats were chronically treated either with the OX26 murine MAb to the rat transferrin receptor or with a mouse IgG2a isotype control (0.25 mg/kg sc daily for 1 week), and the BBB transport of the OX26 MAb was then measured for both rat brain and liver in vivo. Although this treatment regimen resulted in a 41% increase in the permeability-surface area product for 125I-OX26 MAb transport into rat liver in vivo, there was no significant change in the BBB permeability-surface area product for the OX26 MAb. These studies indicate that repetitive administration of cell surface-specific MAbs does not necessarily result in down-regulation of BBB receptors.
Wu
D
D
Department of Medicine, University of California, Los Angeles, School of Medicine, USA.
Pardridge
W M
WM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D011990:Receptors, Transferrin