Noninvasive Detection of Macrophages in Atherosclerotic Lesions Using a Visipaque-Based Nanoparticle Contrast Agent for Computed Tomography

Abstract

This study aimed to evaluate iodinated nanoparticles based on Visipaque for the detection of macrophages in atherosclerotic plaques using computed tomography (CT). The nanoparticles were developed using Visipaque and hydrophobic groups to enhance the macrophages in atherosclerotic lesions. The nanoparticles were measured using NanoSight, and their cellular toxicity was evaluated using the cell counting kit-8 assay. RAW264.7 macrophages were used to detect the cellular uptake of the nanoparticles. Aortic atherosclerotic plaques were induced in New Zealand rabbits (n = 6) by combining a high-cholesterol diet and aortic injury. The noninjured rabbits (n = 4) were fed a normal chow diet and used as controls. CT scans before and 2 h after Visipaque injection, followed by nanoparticle imaging 1 h later. Macrophages were counted using immunohistology with an anti-CD68 monoclonal antibody. The diameter of the nanoparticle agent was approximately 150 mM, and 90% varied broadly between 69 and 248 nm. In vitro experiments demonstrated that the nanoparticles had low cellular toxicity and were effectively endocytosed by macrophages in a time- and dose-dependent manner. In vivo, CT imaging demonstrated that the nanoparticle density was higher in the aortic wall plaques in atherosclerotic rabbits than in control rabbits. The histologic staining confirmed successful atherosclerosis modeling in rabbits and abundant macrophage infiltration in the aortic wall, preferentially taking up the nanoparticles. In conclusion, this study suggests that the novel nanoparticles could be a promising, effective contrast agent for the detection of macrophages in atherosclerotic plaques using CT.