Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo.
Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo.
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发表时间：
1991-10
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通讯作者：
W. Pardridge;J. Buciak;P. Friden
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作者：
W. Pardridge;J. Buciak;P. Friden
体内构成血脑屏障（BBB）的脑毛细血管内皮表达高浓度的转铁蛋白受体，最近的研究表明抗转铁蛋白受体单克隆抗体可能充当BBB药物转运载体。本报告研究了放射性标记抗转铁蛋白受体单克隆抗体在大鼠体内从血流中清除的药代动力学，并评估了与其他外周器官（如肝、肾、心肌或肺）相比，大脑选择性地从血液中提取抗体的程度。 [125I]小鼠免疫球蛋白 G2a 对照抗体以单指数方式被清除，半衰期为 9.8 +/- 2.3 小时。 [3H]OX-26 抗转铁蛋白受体抗体从血液中的清除率为双指数，半衰期为 2.2 +/- 0.8 分钟（清除率的 61 +/- 10%）和 3.9 +/- 0.2 小时（清除率的 39 +/- 4%）。 OX-26抗体在注射后的前60分钟内迅速被肝脏摄取，但这种摄取达到快速饱和，并且肝脏OX-26含量实际上在注射后第一小时后下降。相比之下，大脑不断从血流中提取OX-26抗体，注射后5小时，OX-26的脑内分布容积达到小鼠免疫球蛋白G2a分布容积的18倍。心肌或肺没有对 OX-26 的特异性摄取，观察到肾脏有少量摄取，并且在注射后的前 60 分钟内也达到饱和。（摘要截断为 250 字）
The brain capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo, expresses high concentrations of transferrin receptor, and recent studies show that an antitransferrin receptor monoclonal antibody may function as a BBB drug transport vector. The present report examines the pharmacokinetics of clearance of radiolabeled antitransferrin receptor monoclonal 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. [125I]Mouse immunoglobulin G2a control antibody was cleared monoexponentially with a half-time of 9.8 +/- 2.3 h. The clearance of the [3H]OX-26 antitransferrin receptor antibody from blood was biexponential with half-times of 2.2 +/- 0.8 min (61 +/- 10% of clearance) and 3.9 +/- 0.2 h (39 +/- 4% of clearance). The OX-26 antibody was rapidly taken up by liver during the first 60 min 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 18-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 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)