Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression

Purpose Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis. However, IgG accumulates nonspecifically in atherosclerotic regions, and its accumulation mechanisms have not yet been clarified in detail. Therefore, we explored IgG accumulation mechanisms in atherosclerotic lesions and examined images of radiolabeled IgG for the diagnosis of atherosclerosis. Procedures Mouse IgG without specificity to biomolecules was labeled with technetium-99m via 6-hydrazinonicotinate to yield [ 99m Tc]IgG. ApoE −/− or C57BL/6J mice were injected intravenously with [ 99m Tc]IgG, and their aortas were excised 24 h after injection. After radioactivity measurement, serial aortic sections were autoradiographically and histopathologically examined. RAW264.7 macrophages were polarized into M1 or M2 and then treated with [ 99m Tc]IgG. The radioactivities in the cells were measured after 1 h of incubation. [ 99m Tc]IgG uptake in M1 macrophages was also evaluated after the pretreatment with an anti-Fcγ receptor (FcγR) antibody. The expression levels of FcγRs in the cells were measured by western blot analysis. Results [ 99m Tc]IgG accumulation levels in the aortas were significantly higher in apoE −/− mice than in C57BL/6J mice (5.1 ± 1.4 vs 2.8 ± 0.5 %ID/g, p