Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2325-2330. doi: 10.1073/pnas.1620145114. Epub 2017 Feb 13.

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents.

Wei H¹, Bruns OT¹, Kaul MG², Hansen EC¹, Barch M³, Wiśniowska A⁴, Chen O⁵, Chen Y¹, Li N^3,^6,⁷, Okada S³, Cordero JM¹, Heine M⁸, Farrar CT⁹, Montana DM^1,¹⁰, Adam G², Ittrich H², Jasanoff A^3,^6,⁷, Nielsen P⁸, Bawendi MG¹¹.

Author information

1: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
2: Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Center for Radiology and Endoscopy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
3: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
4: Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139.
5: Department of Chemistry, Brown University, Providence, RI 02912.
6: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139.
7: Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
8: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
9: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.
10: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
11: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; mgb@mit.edu.

Abstract

Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gd-free contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T₁ contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.