title: Exceedingly small iron oxide nanoparticles as positive MRI contrast agents.
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 T1contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: He
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Bruns
authors.affiliation: Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Center for Radiology and Endoscopy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kaul
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Hansen
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Mariya
authors.initials: M
authors.lastname: Barch
authors.affiliation: Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Agata
authors.initials: A
authors.lastname: Wiśniowska
authors.affiliation: Department of Chemistry, Brown University, Providence, RI 02912.
authors.forename: Ou
authors.initials: O
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139.|Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Cordero
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Heine
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Farrar
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.|Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Montana
authors.affiliation: Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Center for Radiology and Endoscopy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Adam
authors.affiliation: Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Center for Radiology and Endoscopy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Ittrich
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139.|Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Alan
authors.initials: A
authors.lastname: Jasanoff
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nielsen
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; mgb@mit.edu.
authors.forename: Moungi G
authors.initials: MG
authors.lastname: Bawendi
mesh_terms: D000418:Albumins / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D052203:Ferrosoferric Oxide / Q000737:chemistry* / Q000493:pharmacokinetics / Q000652:urine; D019786:Gadolinium DTPA / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D019301:Oleic Acid / Q000737:chemistry; D010316:Particle Size; D014018:Tissue Distribution
chemical_list: D000418:Albumins; D003287:Contrast Media; D058185:Magnetite Nanoparticles; C058946:albumin-(gadolinium-DTPA); D019301:Oleic Acid; D019786:Gadolinium DTPA; D052203:Ferrosoferric Oxide
keywords: exceedingly small iron oxide nanoparticles; gadolinium-free positive MR contrast agent; preclinical magnetic resonance imaging; renal clearance