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Multimodality PET/MRI agents targeted to activated macrophages

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 64Cu to generate a PET/MRI probe, and modified with maleic anhydride to increase the negative surface charge. The modified nanoparticulate PET/MRI probe (MDIO-64Cu-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-64Cu-DOTA has an average iron oxide core size of 7–8 nm, an average hydrodynamic diameter of 62.7 nm, an r 1 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-64Cu-DOTA for identification of vulnerable atherosclerotic plaques via the targeting of macrophages.

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Acknowledgments

The authors wish to acknowledge the National Institutes of Health (EB008576-01 and EB000993), the Center for Molecular and Genomic Imaging at the University of California, Davis (U24 CA 110804), and the NMR award of the University of California, Davis for support of this work. We thank Jeongchan Park, Jai Woong Seo, and Ray Wong for help with TEM imaging, zeta potential measurements, and IR spectroscopy, respectively.

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Correspondence to Angelique Y. Louie.

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Responsible Editor: Valerie C. Pierre.

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Tu, C., Ng, T.S.C., Jacobs, R.E. et al. Multimodality PET/MRI agents targeted to activated macrophages. J Biol Inorg Chem 19, 247–258 (2014). https://doi.org/10.1007/s00775-013-1054-9

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Keywords

  • Iron
  • Nanoparticles
  • MRI contrast agents
  • Macrophages
  • Inflammation