Multimodality PET/MRI agents targeted to activated macrophages Topical Issue on Metal-Based MRI Contrast Agents. Guest editor: Valerie C. Pierre

Chuqiao Tu, Thomas S C Ng, Russell E. Jacobs, Angelique Y. Louie

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)247-258
Number of pages12
JournalJournal of Biological Inorganic Chemistry
Volume19
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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