PREPARATION AND BIODISTRIBUTION OF (99M)TECHNETIUM LABELED OXIDIZED LDL IN MAN

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 Tc-99m-LDL was s hown to be feasible in animal models and patients but the clinical uti lity remains to be assessed. Since recent reports suggest that oxidize d LDL may play a major role in the pathogenesis of atherosclerosis, we developed a technique to oxidize autologous LDL and compared the biod istribution of oxidized-LDL with that of native-LDL in man. In additio n, we evaluated the uptake in vivo of oxidized- and native-LDL by athe rosclerotic plaques. LDL, obtained from human plasma was treated with various combinations of copper ions and H2O2 to induce oxidative modif ication by increasing the content of lipid peroxidation products and e lectrophoretic mobility. When LDL (0.3 mg/ml) was incubated with 100 m u M Cu2+ and 500 mu M H2O2 oxidation occurred rapidly within 1 h, and was labelled with Tc-99m efficiently as native LDL. In vivo distributi on 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 trans ient ischemic attacks, revealed accumulation of radiolabelled LDL prep arations in the carotid artery affected by atherosclerotic lesions. We developed a technique to rapidly oxidize LDL using copper and H2O2. B iodistribution data demonstrate that oxidized-LDL is rapidly cleared f rom circulation, is taken up mostly by organs rich in macrophages, and can be detected at the level of carotid plaques.