In vivo metabolism of oxidized low density lipoproteins: Insights from small animal positron emission tomography (PET) studies

The human organism is exposed to numerous processes that generate reactive oxygen or nitrogen species may directly or indirectly cause oxidative modification and damage of proteins. Protein oxidation is regarded as a crucial event in the pathogenesis of various diseases ranging from rheumatoid arthritis to Alzheimer's disease and atherosclerosis. The importance of protein oxidation in respect of altered function is exemplified by oxidation of low density lipoproteins (LDL) which causes altered receptor recognition and, e.g., plays a key role in atherogenesis. However, data concerning the role of circulation oxidized LDL (oxLDL) in the development and outcome of disease are scarce. One reason for this is the shortage of methods for direct assessment of the metabolic fate of circulation oxLDL in vivo. As an attractive alternative to, e.g., LDL iodination methods, a novel methodology based on the radiolabeling of apoB-100 of native LDL (nLDL) and oxLDL, respectively, with the positron emitter fluorine-18 (¹⁸F]SFB) was developed. In cotrast to most protein radioiodination methods, radiolabeling of both nLDL and oxLDL using [¹⁸F]SFB caused neither additional oxidative structural modifications of LDLlipids and proteins nor alteration of their biological activity and functionality, respectively, in virto. The method was further evaluated with respect to the radiopharmacological properties to both [¹⁸F]fluorobenzoylated nLDL and oxLDL by biodistribution and dynamic positron emission tomography (PET) studies in male Wistar rats. These studies demonstrated the methodology to be of value to characterize and to discriminate the kinetics and the metabolic fate of nLDL and oxLDL in small animals in vivo.