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    Molecular Magnetic Resonance Imaging of Nitric Oxide in Biological Systems
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    • Ali Barandov
      Ali Barandov
      Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
      More by Ali Barandov
    • Souparno Ghosh
      Souparno Ghosh
      Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
      More by Souparno Ghosh
    • Nan Li
      Nan Li
      Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
      More by Nan Li
    • Benjamin B. Bartelle
      Benjamin B. Bartelle
      Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
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    • Jade I. Daher
      Jade I. Daher
      Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
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    • Michael L. Pegis
      Michael L. Pegis
      Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
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      Orcidhttp://orcid.org/0000-0001-6686-1717
    • Hannah Collins
      Hannah Collins
      Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
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    • Alan Jasanoff*
      Alan Jasanoff
      Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
      Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
      Department of Nuclear Science & Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Rm. 16-561, Cambridge, Massachusetts 02139, United States
      *Email: [email protected]. Phone: 617-452-2538.
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      Orcidhttp://orcid.org/0000-0002-2834-6359
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    ACS Sensors

    Cite this: ACS Sens. 2020, 5, 6, 1674–1682
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    https://doi.org/10.1021/acssensors.0c00322
    Published May 21, 2020
    Copyright © 2020 American Chemical Society
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    Abstract

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    Detection of nitric oxide (NO) in biological systems is challenging due to both physicochemical properties of NO and limitations of current imaging modalities and probes. Magnetic resonance imaging (MRI) could be applied for studying NO in living tissue with high spatiotemporal resolution, but there is still a need for chemical agents that effectively sensitize MRI to biological NO production. To develop a suitable probe, we studied the interactions between NO and a library of manganese complexes with various oxidation states and molecular structures. Among this set, the manganese(III) complex with N,N′-(1,2-phenylene)bis(5-fluoro-2-hydroxybenzamide) showed favorable changes in longitudinal relaxivity upon addition of NO-releasing chemicals in vitro while also maintaining selectivity against other biologically relevant reactive nitrogen and oxygen species, making it a suitable NO-responsive contrast agent for T1-weighted MRI. When loaded with this compound, cells ectopically expressing nitric oxide synthase (NOS) isoforms showed MRI signal decreases of over 20% compared to control cells and were also responsive to NOS inhibition or calcium-dependent activation. The sensor could also detect endogenous NOS activity in antigen-stimulated macrophages and in a rat model of neuroinflammation in vivo. Given the key role of NO and associated reactive nitrogen species in numerous physiological and pathological processes, MRI approaches based on the new probe could be broadly beneficial for studies of NO-related signaling in living subjects.

    Copyright © 2020 American Chemical Society

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    This article is cited by 22 publications.

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    14. Ali Barandov, Souparno Ghosh, Alan Jasanoff. Probing nitric oxide signaling using molecular MRI. Free Radical Biology and Medicine 2022, 191 , 241-248. https://doi.org/10.1016/j.freeradbiomed.2022.08.042
    15. Jason Yun, Michelle Baldini, Rochishnu Chowdhury, Arnab Mukherjee. Designing Protein‐Based Probes for Sensing Biological Analytes with Magnetic Resonance Imaging. Analysis & Sensing 2022, 2 (5) https://doi.org/10.1002/anse.202200019
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    17. He Wei, Abigail M Frey, Alan Jasanoff. Molecular fMRI of neurochemical signaling. Journal of Neuroscience Methods 2021, 364 , 109372. https://doi.org/10.1016/j.jneumeth.2021.109372
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    19. Ning Wang, Tingting Wang, Xinxin Zhao, Yulan Chen, Ruixia Liu, Yu Fang, Rui Zhang. Molecular characterization of the nitric oxide synthase gene and its immunomodulation of nitric oxide production in the triangle shell mussel (Hyriopsis cumingii). Developmental & Comparative Immunology 2021, 122 , 104136. https://doi.org/10.1016/j.dci.2021.104136
    20. Andrew Tamis, Corina S. Drapaca. Modeling NO Biotransport in Brain Using a Space-Fractional Reaction-Diffusion Equation. Frontiers in Physiology 2021, 12 https://doi.org/10.3389/fphys.2021.644149
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    22. Sara Lacerda, Daouda Ndiaye, Éva Tóth. MRI relaxation agents based on transition metals. 2021, 109-142. https://doi.org/10.1016/bs.adioch.2021.06.001
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    ACS Sensors

    Cite this: ACS Sens. 2020, 5, 6, 1674–1682
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acssensors.0c00322
    Published May 21, 2020
    Copyright © 2020 American Chemical Society
    Request reuse permissions

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