Visualization of Macrophage Recruitment to Inflammation Lesions using Highly Sensitive and Stable Radionuclide-Embedded Gold Nanoparticles as a Nuclear Bio-Imaging Platform

Abstract

Reliable and sensitive imaging tools are required to track macrophage migration and provide a better understating of their biological roles in various diseases. Here, we demonstrate the possibility of radioactive iodide-embedded gold nanoparticles (RIe-AuNPs) as a cell tracker for nuclear medicine imaging. To demonstrate this utility, we monitored macrophage migration to carrageenan-induced sites of acute inflammation in living subjects and visualized the effects of anti-inflammatory agents on this process. Macrophage labeling with RIe-AuNPs did not alter their biological functions such as cell proliferation, phenotype marker expression, or phagocytic activity. In vivo imaging with positron-emission tomography revealed the migration of labeled macrophages to carrageenan-induced inflammation lesions 3 h after transfer, with highest recruitment at 6 h and a slight decline of radioactive signal at 24 h; these findings were highly consistent with the data of a bio-distribution study. Treatment with dexamethasone (an anti-inflammation drug) or GSK5182 (an ERRγ inverse agonist) hindered macrophage recruitment to the inflamed sites. Our findings suggest that a cell tracking strategy utilizing RIe-AuNPs will likely be highly useful in research related to macrophage-related disease and cell-based therapies.

Multifunctional Nanohybrid Based on Porous Silicon Nanoparticles, Gold Nanoparticles, and Acetalated Dextran for Liver Regeneration and Acute Liver Failure Theranostics

“…The high atomic number and electron density of Au make it a good candidate for CT imaging, hence applying Au NP‐based nanohybrids is highly potent for hepatic disease theranostics. Several papers have demonstrated the feasibility of applying CT imaging to track monocyte recruitment to tissue plaques using Au NPs as contrasting agent, and the contrasting efficiency of Au NPs is largely related with its particle size: Too small Au NPs (<5 nm) suffer from rapid clearance by renal filtration, leading to low plaque accumulation, and they also tend to show limited monocyte phagocytic system (MPS) uptake, resulting in an unsatisfied lesion tracking ability; whereas larger Au NPs (>150 nm), despite their satisfied MPS uptake and contrasting ability, can hardly be excreted from the body and show higher cellular toxicity . To address this obstacle, it is desirable that the initial size of Au NPs is relatively small with high biocompatibility and further be incorporated into a larger biodegradable/biocompatible matrix to reduce renal clearance and improve macrophages uptake.…”

A comparative study of hydrophilic phosphine hexanuclear rhenium cluster complexes’ toxicity

“…cardiovascular disease, in particular ischemia, arthritis and other inflammation processes) and therapies. 21 , 22 …”

Cell Tracking in Cancer Immunotherapy

“…In vivo studies have analyzed the biological role and migration of macrophages using different imaging methods such as fluorescent imaging (97), PET, MRI, and multimodal imaging. Macrophages migration to the inflammatory site after an induction of inflammation was analyzed by in vitro labeling with radioactive iodide-embedded gold nanoparticles (RIe-AuNPs) and PET imaging (76). During inflammatory disease such as arthritis, atherosclerotic plaques, in vivo staining of the macrophage with 111 In-or 64 Cu-labeled antibodies allowed imaging follow-up, evaluation of therapeutic efficacy and therapy adaption (98,99).…”