PHARMACOKINETICS AND BLOOD-BRAIN-BARRIER TRANSPORT OF AN ANTITRANSFERRIN 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 ca pillary endothelium, which makes up the blood-brain barrier (BBB) in v ivo, are brain drug-delivery vectors. When cells are chronically expos ed to MAbs in tissue culture, there is often down-regulation of the ce ll surface receptors. To examine whether similar down-regulation occur s in vivo, rats were chronically treated either with the OX26 murine M Ab to the rat transferrin receptor or with a mouse IgG2a isotype contr ol (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 I-125-OX26 MAb transport into rat liver in vi vo, there was no significant change in the BBB permeability-surface ar ea product for the OX26 MAb. These studies indicate that repetitive ad ministration of cell surface-specific MAbs does not necessarily result in down-regulation of BBB receptors.