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Multimodality PET/MRI agents targeted to activated macrophages
Chuqiao Tu1, Thomas S C Ng, Russell E Jacobs
1Department of Biomedical Engineering, University of California, Davis, Davis, CA, 95616, USA.
Abstract:
The recent emergence of multimodality imaging, particularly the combination of PET and MRI, has led to excitement over the prospect of improving detection of disease. Iron oxide nanoparticles have become a popular platform for the fabrication of PET/MRI probes owing to their advantages of high MRI detection sensitivity, biocompatibility, and biodegradability. In this article, we report the synthesis of dextran-coated iron oxide nanoparticles (DIO) labeled with the positron emitter (64)Cu to generate a PET/MRI probe, and modified with maleic anhydride to increase the negative surface charge. The modified nanoparticulate PET/MRI probe (MDIO-(64)Cu-DOTA) bears repetitive anionic charges on the surface that facilitate recognition by scavenger receptor type A (SR-A), a ligand receptor found on activated macrophages but not on normal vessel walls. MDIO-(64)Cu-DOTA has an average iron oxide core size of 7-8 nm, an average hydrodynamic diameter of 62.7 nm, an r1 relaxivity of 16.8 mM(-1) s(-1), and an r 2 relaxivity of 83.9 mM(-1) s(-1) (37 °C, 1.4 T). Cell studies confirmed that the probe was nontoxic and was specifically taken up by macrophages via SR-A. In comparison with the nonmodified analog, the accumulation of MDIO in macrophages was substantially improved. These characteristics demonstrate the promise of MDIO-(64)Cu-DOTA for identification of vulnerable atherosclerotic plaques via the targeting of macrophages.
Insights
Researchers developed a novel PET/MRI probe using iron oxide nanoparticles. This new probe, MDIO-(64)Cu-DOTA, targets macrophages, showing promise for detecting vulnerable atherosclerotic plaques.
Area of Science:
- Nanotechnology
- Biomedical Imaging
- Materials Science
Background:
- Multimodality imaging, especially PET/MRI, offers improved disease detection.
- Iron oxide nanoparticles are suitable for PET/MRI probes due to high MRI sensitivity and biocompatibility.
Purpose of the Study:
- To synthesize and characterize a novel PET/MRI probe for enhanced disease detection.
- To develop a probe targeting macrophages for identifying vulnerable atherosclerotic plaques.
Main Methods:
- Synthesis of dextran-coated iron oxide nanoparticles (DIO) labeled with 64Cu.
- Modification of nanoparticles with maleic anhydride to create anionic charges (MDIO-(64)Cu-DOTA).
- Characterization of probe size, relaxivity, and in vitro macrophage uptake via scavenger receptor type A (SR-A).
Main Results:
- The MDIO-(64)Cu-DOTA probe exhibited specific uptake by macrophages through SR-A.
- In vitro studies confirmed the probe's non-toxicity.
- The modified probe showed significantly improved accumulation in macrophages compared to the non-modified version.
Conclusions:
- MDIO-(64)Cu-DOTA is a promising PET/MRI probe for macrophage targeting.
- The probe facilitates the identification of vulnerable atherosclerotic plaques.
- Surface modification enhances probe accumulation in target macrophages.
