Membrane-Permeable Mn(III) Complexes for Molecular Magnetic Resonance Imaging of Intracellular Targets
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Barandov_041116JACS_main-Jasanoff.pdf
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main article
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Author(s)
Barandov, Ali
Gonzalez, Beatriz A.
White, William L.
Lippard, Stephen J.
Jasanoff, Alan Pradip
Bartelle, Benjamin B.
Date Issued
April 2016
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Barandov, Ali; Bartelle, Benjamin B.; Gonzalez, Beatriz A.; White, William L.; Lippard, Stephen J. and Jasanoff, Alan. “Membrane-Permeable Mn(III) Complexes for Molecular Magnetic Resonance Imaging of Intracellular Targets.” Journal of the American Chemical Society 138, no. 17 (May 2016): 5483–5486 © 2016 American Chemical Society
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Author's final manuscript
Abstract
Intracellular compartments make up roughly two-thirds of the body, but delivery of molecular imaging probes to these spaces can be challenging. This situation is particularly true for probes designed for detection by magnetic resonance imaging (MRI), a high-resolution but relatively insensitive modality. Most MRI contrast agents are polar and membrane impermeant, making it difficult to deliver them in sufficient quantities for measurement of intracellular analytes. Here we address this problem by introducing a new class of planar tetradentate Mn(III) chelates assembled from a 1,2-phenylenediamido (PDA) backbone. Mn(III)-PDA complexes display T₁ relaxivity comparable to that of Gd(III)-based contrast agents and undergo spontaneous cytosolic localization via defined mechanisms. Probe variants incorporating enzyme-cleavable acetomethoxy ester groups are processed by intracellular esterases and accumulate in cells. Probes modified with ethyl esters preferentially label genetically modified cells that express a substrate-selective esterase. In each case, the contrast agents gives rise to robust T₁-weighted MRI enhancements, providing precedents for the detection of intracellular targets by Mn(III)-PDA complexes. These compounds therefore constitute a platform from which to develop reagents for molecular MRI of diverse processes inside cells.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Nuclear Science and Engineering
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DOI of Published Version
https://doi.org/10.1021/jacs.5b13337
