TY - JOUR
T1 - Membrane-permeable Mn(III) complexes for molecular magnetic resonance imaging of intracellular targets
AU - Barandov, Ali
AU - Bartelle, Benjamin B.
AU - Gonzalez, Beatriz A.
AU - White, William L.
AU - Lippard, Stephen J.
AU - Jasanoff, Alan
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/5/4
Y1 - 2016/5/4
N2 - 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 highresolution 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.
AB - 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 highresolution 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.
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U2 - 10.1021/jacs.5b13337
DO - 10.1021/jacs.5b13337
M3 - Article
C2 - 27088782
AN - SCOPUS:84969247782
SN - 0002-7863
VL - 138
SP - 5483
EP - 5486
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 17
ER -