title: A Janus Chelator Enables Biochemically Responsive MRI Contrast with Exceptional Dynamic Range.
abstract: We introduce a new biochemically responsive Mn-based MRI contrast agent that provides a 9-fold change in relaxivity via switching between the Mn3+and Mn2+oxidation states. Interchange between oxidation states is promoted by a "Janus" ligand that isomerizes between binding modes that favor Mn3+or Mn2+. It is the only ligand that supports stable complexes of Mn3+and Mn2+in biological milieu. Rapid interconversion between oxidation states is mediated by peroxidase activity (oxidation) and l-cysteine (reduction). This Janus system provides a new paradigm for the design of biochemically responsive MRI contrast agents.
authors.affiliation: The Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , 149 Thirteenth Street, Suite 2301, Charlestown, Massachusetts 02129, United States.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Gale
authors.affiliation: The Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , 149 Thirteenth Street, Suite 2301, Charlestown, Massachusetts 02129, United States.
authors.forename: Chloe M
authors.initials: CM
authors.lastname: Jones
authors.affiliation: The Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , 149 Thirteenth Street, Suite 2301, Charlestown, Massachusetts 02129, United States.
authors.forename: Ian
authors.initials: I
authors.lastname: Ramsay
authors.affiliation: The Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , 149 Thirteenth Street, Suite 2301, Charlestown, Massachusetts 02129, United States.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Farrar
authors.affiliation: The Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , 149 Thirteenth Street, Suite 2301, Charlestown, Massachusetts 02129, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Caravan
mesh_terms: D002614:Chelating Agents / Q000737:chemistry* / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D008345:Manganese; D009195:Peroxidase; D003545:Cysteine