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Updated: Jun 7, 2026
Microwave-driven Synthesis of Iron Oxide Nanoparticles for Fast Detection of Atherosclerosis
Published on: March 22, 2016
Imaging monocytes with iron oxide nanoparticles targeted towards the monocyte integrin MAC-1 (CD11b/CD18) does not
C von zur Muhlen1, A Fink-Petri, J Salaklang
1Department of Cardiology and Angiology, University of Freiburg, Freiburg, Germany. constantin.vonzurmuehlen@uniklinik-freiburg.de
Abstract:
Imaging of macrophages with superparamagnetic iron oxide particles (SPIO) has been performed to improve detection of atherosclerotic plaque inflammation in human and mouse studies by molecular magnetic resonance imaging (MRI). Since affinity of the monocyte/macrophage integrin MAC-1 (CD11b/CD18) is upregulated in inflammation, we generated a contrast agent targeting CD11b (CD11b-SPIOs) for improved macrophage detection in plaques. CD11b-SPIOs and non-targeted SPIOs (control-SPIOs) were incubated in vitro with human monocytes/macrophages. As quantified by SPIO-induced MRI signal extinction, intracellular iron-content was significantly higher in monoytes/macrophages incubated with CD11b-SPIO than with control-SPIO in vitro (p < 0.05), suggesting an improved uptake of CD11b-SPIOs into monocytes. Therefore, the aortic arch (AA) and vessel branches of ApoE(-/-)-knockout mice on a Western-type diet were imaged before and 48 h after contrast agent injection of either CD11b-SPIOs or control-SPIOs, using a 9.4 T animal MRI system. The SPIO-induced change in the MRI signal was quantified, as well as the macrophage-content by anti-CD68 immunhistochemistry and the iron-content by Prussian-blue staining. However, SPIO-induced signal extinction in in vivo-MRI was similar in CD11b-SPIO and control-SPIO-injected animals, with a non-significant trend towards an improved uptake of CD11b-SPIOs in the subclavian artery and subsections of the AA. These data correlated well with the results obtained by histology. Although in vitro MRI-data indicated an increased uptake of targeted CD11b-SPIOs in monocytes/macrophages, in vivo mouse data do not allow improved atherosclerotic plaque detection compared WITH non-targeted SPIOs. Therefore, CD11b-targeted MRI contrast labelling of monocytes/macrophages does not seem to be a successful strategy in stable atherosclerotic plaques such as found in the ApoE(-/-)-knockout-model. However, the impressive correlation between MRI and histology data encourages further development of inflammation- and plaque-specific contrast agents for vulnerable plaque imaging.
Insights
Targeted superparamagnetic iron oxide particles (SPIOs) showed improved in vitro macrophage uptake but failed to enhance in vivo atherosclerotic plaque detection in mice. Further development of plaque-specific contrast agents is encouraged for vulnerable plaque imaging.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Cardiovascular Research
Background:
- Atherosclerotic plaque inflammation is a key driver of cardiovascular events.
- Molecular magnetic resonance imaging (MRI) using superparamagnetic iron oxide particles (SPIOs) offers potential for detecting plaque inflammation.
- Targeting macrophage-specific markers like CD11b can enhance SPIO uptake in inflammatory cells.
Purpose of the Study:
- To develop and evaluate CD11b-targeted SPIOs for improved macrophage detection in atherosclerotic plaques.
- To assess the in vitro and in vivo efficacy of CD11b-SPIOs compared to non-targeted SPIOs for molecular MRI.
Main Methods:
- Generation of CD11b-targeted SPIOs (CD11b-SPIOs) and non-targeted control SPIOs (control-SPIOs).
- In vitro incubation of CD11b-SPIOs and control-SPIOs with human monocytes/macrophages, followed by MRI assessment of iron uptake.
- In vivo MRI of ApoE(-/-)-knockout mouse aortas before and after contrast agent injection, correlated with histology (CD68 staining and Prussian-blue staining).
Main Results:
- In vitro studies showed significantly higher intracellular iron content in monocytes/macrophages incubated with CD11b-SPIOs compared to control-SPIOs.
- In vivo MRI revealed similar SPIO-induced signal extinction between CD11b-SPIO and control-SPIO groups in atherosclerotic mouse models.
- Histological analysis confirmed the MRI findings, showing no significant improvement in plaque detection with targeted SPIOs in vivo.
Conclusions:
- CD11b-targeted SPIOs did not improve in vivo detection of stable atherosclerotic plaques in the ApoE(-/-)-knockout mouse model.
- While in vitro data suggested enhanced uptake, in vivo results indicate limitations for this specific targeting strategy in stable plaques.
- The strong correlation between MRI and histology supports continued research into developing effective inflammation- and plaque-specific contrast agents for vulnerable plaque imaging.
