Radioimaging Foam Cells Infiltrating Atherosclerotic Plaques in Mice Using 125I-labeled oxLDL as a Radiotracer

Abstract

Bioimaging such as magnetic resonance is used to monitor atherosclerotic plaques consisting of foam cells, which are derived from macrophages that have ingested oxidized low-density lipoprotein (oxLDL). However, the current bioimaging techniques are not highly specific and sensitive in detecting foam cells, calling for the development of higher precision foam cell detection probes. Here, we investigated the utility of iodine-125-labeled oxLDL (¹²⁵I-oxLDL) as a prototype radiotracer in the radioimaging of foam cells infiltrating atherosclerotic plaques. Mouse bone marrow-derived macrophages (BMDMs) were used to analyze oxLDL uptake. Atherosclerosis mouse model was injected with ¹²⁵I-oxLDL and DiI-labeled oxLDL (DiI-oxLDL). Accumulation of ¹²⁵I-oxLDL and DiI-oxLDL in foam cells infiltrating atherosclerotic plaques was examined using Oil Red O (ORO) staining, autoradiography, and fluorescent immunohistochemistry. BMDMs phagocytosed oxLDL/¹²⁵I-oxLDL via CD36, but not LDL/¹²⁵I-LDL. The radioactive signal from ¹²⁵I-oxLDL phagocytosed by the BMDMs could be detected for at least 3 days. In atherosclerosis mouse model, atherosclerotic plaques formed in the aortic arches and valves. The radioactive signal of the injected ¹²⁵I-oxLDL was detected in atherosclerotic plaques of the aortic arch, and its intensity was positively correlated with the lesion size. Furthermore, the DiI-oxLDL fluorescent signals were detected in foam cells accumulating in atherosclerotic plaques. Thus, we found that ¹²⁵I-oxLDL can be used as a radiotracer in the radioimaging of foam cells in atherosclerotic plaques by autoradiography, suggesting its potential future applications in bioimaging methods such as single-photon emission computed tomography.