The brain capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo, expresses high concentrations of transfernn receptor, and recent studies show that an antitransfernn receptor monodonal anthody may funcfion as a BBB drug transport vector. The present report examines the pharmacokinetics of dearance of radiolabeled antitransfertin receptor monodonal antibody from the bloodstream in rats in vivo, and also assesses the extent to which brain selectively extracts the antibody from the blood compared to other peripheral organs such as liver, kidney, myocardium, or lung.[‘l] Mouse immunoglobulin G2a control antibody was deared monoexponentially wfth a half-tune of 9.8±2.3 h. The clearance of the [3H] OX-26 antitransfernn receptor antibody from blood was blexponentlal with haif-thies of2. 2±O. 8min (61±1O% ofciearance) and3. 9±O. 2h (39±

4% of dearance). The OX-26 anthody was rapklly taken up by liver during the first 60 mm after injection, but this uptake reached rapid saturation, and hepatic OX-26 content actually declined subsequent to the first hour after injection. In contrast, brain continuously extracted the OX-26 antibody from the bloodstream, and the brain volume of distribution of OX-26 reached a value 1 8-fold greater than the volume of distribution of the mouse immunoglobulin G2a at 5 h after injection. There was no specific uptake of the OX-26 by myocardium or lung, and minor uptake by kidney was observed that also reached saturation within the first 60 mm after injectlon. Studies with isdated brain CapIeS showed the OX-26 antibody bound equaky well to human, bo-vine, or rat brain capillaries, and the binding was fime-dependet, temperature-dependent, saturable, and succeeded by endocy-tosis. In conclusion, these studies demonstrate that an antitransfenin receptor antibody selectively targets brain relative to or-gans such as kidney, heart, or lung. The pharmacokinetic analy-sis shows that the blood level of the monoclonal antibody is maintained relatively constant after initial rapid dearance of the antibody by liver.