Iuliano L, Signore A, Vallabajosula S, Colavita A R, Camastra C, Ronga G, Alessandri C, Sbarigia E, Fiorani P, Violi F
Institute of Clinical Medicine I, University La Sapienza, Rome, Italy.
Atherosclerosis. 1996 Sep 27;126(1):131-41. doi: 10.1016/0021-9150(96)05888-1.
Radiolabelled autologous low density lipoprotein (LDL) has previously been used to study in vivo distribution and metabolism of native-LDL. Non-invasive imaging of atherosclerotic lesions using 99mTc-LDL was shown to be feasible in animal models and patients but the clinical utility remains to be assessed. Since recent reports suggest that oxidized LDL may play a major role in the pathogenesis of atherosclerosis, we developed a technique to oxidize autologous LDL and compared the biodistribution of oxidized-LDL with that of native-LDL in man. In addition, we evaluated the uptake in vivo of oxidized- and native-LDL by atherosclerotic plaques. LDL, obtained from human plasma was treated with various combinations of copper ions and H2O2 to induce oxidative modification by increasing the content of lipid peroxidation products and electrophoretic mobility. When LDL (0.3 mg/ml) was incubated with 100 microM Cu2+ and 500 microM H2O2 oxidation occurred rapidly within 1 h, and was labelled with 99mTc efficiently as native LDL. In vivo distribution studies revealed a faster plasma clearance of oxidized-LDL compared to native-LDL, and a higher uptake by the reticuloendothelial system. Tomographic scintigraphy of the neck in patients suffering from transient ischemic attacks, revealed accumulation of radiolabelled LDL preparations in the carotid artery affected by atherosclerotic lesions. We developed a technique to rapidly oxidize LDL using copper and H2O2. Biodistribution data demonstrate that oxidized-LDL is rapidly cleared from circulation, is taken up mostly by organs rich in macrophages, and can be detected at the level of carotid plaques.
放射性标记的自体低密度脂蛋白（LDL）此前已被用于研究天然LDL的体内分布和代谢。使用99mTc-LDL对动脉粥样硬化病变进行无创成像在动物模型和患者中已被证明是可行的，但临床效用仍有待评估。由于最近的报告表明氧化型LDL可能在动脉粥样硬化的发病机制中起主要作用，我们开发了一种氧化自体LDL的技术，并比较了氧化型LDL与人天然LDL的生物分布。此外，我们评估了动脉粥样硬化斑块对氧化型和天然LDL的体内摄取情况。从人血浆中获得的LDL用铜离子和H2O2的各种组合进行处理，通过增加脂质过氧化产物的含量和电泳迁移率来诱导氧化修饰。当LDL（0.3mg/ml）与100μM Cu2+和500μM H2O2一起孵育时，1小时内迅速发生氧化，并能像天然LDL一样有效地用99mTc标记。体内分布研究表明，与天然LDL相比，氧化型LDL的血浆清除更快，并且网状内皮系统对其摄取更高。对短暂性脑缺血发作患者颈部进行断层闪烁扫描，发现放射性标记的LDL制剂在受动脉粥样硬化病变影响的颈动脉中积聚。我们开发了一种使用铜和H2O2快速氧化LDL的技术。生物分布数据表明，氧化型LDL能迅速从循环中清除，主要被富含巨噬细胞的器官摄取，并且可以在颈动脉斑块水平检测到。
