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Molecular Magnetic Resonance Imaging of Nitric Oxide in Biological Systems
Name
nihms-1610354.pdf
Description
Accepted version
Size
1.1 MB
Format
Adobe PDF
Checksum (MD5)
d5165a363ebffdd179b0cb49e88add98
Author(s)
Barandov, Ali
Ghosh, Souparno
Li, Nan
Bartelle, Benjamin B
Daher, Jade I
Pegis, Michael L
Collins, Hannah
Jasanoff, Alan
Date Issued
2020
Journal
ACS Sensors
Publisher
American Chemical Society (ACS)
Citation
Barandov, Ali, Ghosh, Souparno, Li, Nan, Bartelle, Benjamin B, Daher, Jade I et al. 2020. "Molecular Magnetic Resonance Imaging of Nitric Oxide in Biological Systems." ACS Sensors, 5 (6).
Version
Author's final manuscript
Abstract
Copyright © 2020 American Chemical Society. 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.
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
10.1021/ACSSENSORS.0C00322
