Combined Fluorescence and Magnetic Resonance Imaging of Primary Macrophage Migration to Sites of Acute Inflammation Using Near-Infrared Fluorescent Magnetic Nanoparticles

Purpose: This study aimed to track the migration of primary macrophages labeled with near-infrared (NIR) fluorescent magnetic nanoparticles toward chemically induced acute inflammatory lesions in mice and to visualize the effect of anti-inflammatory drugs on macrophage migration using combined fluorescence and magnetic resonance imaging (FLI/MRI). Procedures: Primary macrophages were labeled with NIR fluorescent magnetic nanoparticles, and labeled cells were injected into mice intravenously. One day later, inflammation was induced by subcutaneous injection of 1 % carrageenan (CG) solution to footpads of the right hind leg, and phosphate-buffered saline (PBS) as control treatment was subcutaneously injected to footpad of the left hind leg. To evaluate the effect of drug treatment on macrophage migration, a single dose of dexamethasone (DEX) was intraperitoneally administered to the mice immediately after the induction of inflammation and was followed by combined FLI/MRI at predetermined time points. Results: No difference in cellular viability or phagocytic activity was observed between the labeled and parent macrophages. In vivo optical imaging revealed an increase in FLI signals in CG-injected footpads in a time-dependent manner, but not in PBS-treated footpads. DEX treatment inhibited the migration of the labeled macrophages to the CG-injected footpads, with relative decreases in FLI activity. In accordance with FLI, T₂*-weighted MR images showed hypo-intense signals in the CG-injected footpads but not in the PBS-injected footpads. The DEX-treated mice did not show a dark signal loss zone on MR images in the CG-treated paw. Conclusions: We successfully tracked the migration of macrophages to inflammatory lesions using both FLI and MRI with NIR fluorescent magnetic nanoparticles and demonstrated the inhibitory effects of DEX on macrophage migration to inflammation sites.