Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 9, Pages 2325-2330Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1620145114
Keywords
exceedingly small iron oxide nanoparticles; renal clearance; gadolinium-free positive MR contrast agent; preclinical magnetic resonance imaging
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Funding
- Massachusetts Institute of Technology (MIT)-Harvard NIH Center for Cancer Nanotechnology Excellence Grant [1U54-CA119349]
- Army Research Office through the Institute for Soldier Nanotechnologies [W911NF-07-D-0004]
- NIH [9-P41-EB015871-26A1, R01-MH103160, R01-DA028299]
- MIT Deshpande Center Innovation Grant
- European Union Seventh Framework Programme (FP7) Project RESOLVE [FP7-HEALTH-2012-305707]
- European Molecular Biology Organization long-term fellowship
- National Science Foundation graduate fellowship
- Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad
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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 similar to 3-nm inorganic cores and similar to 1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T-1 contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.
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