Biodistributions of air-filled albumin microspheres in rats and pigs.
Biodistributions of air-filled albumin microspheres in rats and pigs.
复制标题
充气白蛋白微球在大鼠和猪体内的生物分布。
作者：
Per Walday;Helge Tolleshaug;Helge Tolleshaug;T. Gjøen;G. Kindberg;T. Berg;T. Skotland;Eckart Holtz
超声造影剂Albunex的空气填充微球的独特之处在于，其壁由人血清白蛋白分子组成，所述人血清白蛋白分子通过对白蛋白溶液进行超声处理而变得不可溶。通过浮选分离微球，并用125 I标记洗涤的微球。标记物质主要以颗粒形式从循环中清除，而不是以可溶性白蛋白分子形式清除。在大鼠中，80%的静脉注射微球在2分钟内从血液中清除。近60%的剂量在肝脏中回收，仅5%在肺中，9%在脾中，肾脏，心脏和大脑中的量可以忽略不计。在肝脏中，超过90%的放射性被枯否细胞（肝脏巨噬细胞）吸收。肝脏中的蛋白质降解明显符合一级动力学（半衰期40 min）。在猪中，超过90%的静脉注射剂量在肺中回收。与大鼠相比，猪肺中的回收率大幅增加，可能是由于猪的肺血管内巨噬细胞;在大鼠（或人）的该位置通常不存在巨噬细胞。在大鼠的一系列单独实验中，检查了来自微球的壳材料的生物分布。通过对悬浮液施加外部压力使微球塌陷，留下可沉淀的蛋白质材料，其由气泡周围的“壳”中的不溶性白蛋白层组成。“壳”和微球从循环中清除，并以相同的动力学被肝脏吸收。在肺中，回收的壳的比例（15%）高于微球。
The air-filled microspheres of the ultrasound-contrast agent Albunex are unique in that the walls consist of human serum albumin molecules which have been made insoluble by sonication of the albumin solution. The microspheres were isolated by flotation, and the washed microspheres were labelled with 125I. The labelled material was cleared from the circulation mainly as particles, not as soluble albumin molecules. In rats, 80% of intravenously injected microspheres were cleared from the blood within 2 min. Nearly 60% of the dose was recovered in the liver, only 5% in the lungs, 9% in the spleen, and negligible quantities in kidneys, heart and brain. Of the radioactivity in the liver, more than 90% was taken up by Kupffer cells (liver macrophages). The protein in the liver was degraded apparently with first-order kinetics (half-life 40 min). In pigs, over 90% of the intravenously injected dose was recovered in the lungs. The vastly increased recovery in pig lungs, compared with that in rats, is probably due to the pulmonary intravascular macrophages of the pig; macrophages are not normally found in this location in rats (or humans). In a separate series of experiments in rats, the biodistribution of shell material from the microspheres was examined. The microspheres were made to collapse by applying external pressure on the suspension, leaving sedimentable protein material consisting of layers of insoluble albumin from the 'shells' surrounding the air bubble. The 'shells' and the microspheres were cleared from the circulation and taken up by the liver with the same kinetics. In the lungs, a higher proportion (15%) of shells than of microspheres was recovered.