| 초록 |
Brain drug targeting through the blood-brain barrier (BBB) in vivo is possible with peptidornirnetic monoclonal antibodies that undergo receptor-mediated transcytosis through the BBB. Monoclonal antibody to the rat transferrin receptor, such as the OX26 was studied in rats as a transport vector through BBB on the transferrin receptor. But, OX26 is not an effective brain delivery vector in mouse. In the present studies, rat monoclonal antibody, 8D3 to the mouse transferrin receptor were evaluated for brain drug targeting vector intransgenic mouse model. Pharrnacokinetic parameters in plasma and organ uptakes were determined at varioustimes after i.v. bolus injection of [ $^{}125}I$ ] 8D3 in Balb/c mice. Brain uptake of [ $^{}125}I$ ] 8D3 was also studied with an internal carotid artery perfusioncapillary depletion method. After i.v. injection of [ $^{}125}I$ ] 8D3, plasma concentrations declined biexponentially with elimination half lift of approximately 2.2 hours. Brain uptake of [ $^{}125}I$ ] 8D3 was $0.50{ pm}0.09$ persent of injected dose per g brain after 2 hours i.v. injection. After perfusion 5 min the apparent volume of distibution of [ $^{}125}I$ ] 8D3 in brain was $22.3 { mu}l/g,$ which was 4.8 fold higher than the intravascular volume. These studies indicate rat monoclonal antibody to the mouse transferrin receptor, 8D3 may be used for brain drug targeting vector in mice. |
