TY - JOUR
T1 - A Responsive Magnetic Resonance Imaging Contrast Agent for Detection of Excess Copper(II) in the Liver in Vivo
AU - Paranawithana, Namini N.
AU - Martins, Andre F.
AU - Clavijo Jordan, Veronica
AU - Zhao, Piyu
AU - Chirayil, Sara
AU - Meloni, Gabriele
AU - Dean Sherry, A.
N1 - Funding Information:
Financial support from the National Institutes of Health (DK-095416 and EB-015908), the American Diabetes Association (ADA 7-12-IN-42), and the Robert A. Welch Foundation (AT-584 to ADS and AT-1935-20170325 to GM) is gratefully acknowledged. We thank the staff at Beamline 9-3, Stanford Synchrotron Radiation Light Source (SSRL), for support in XAS data collection. We also thank Dr. Alexendar Funk for help with the mouse imaging experiments at UTSW, Drs. Hien Q. Nguyen and Alexios Papadimitrators for their support and training in the ICP-MS, EPR experiments at UT Dallas, and Dr. Limei Zhang at University of Nebraska—Lincoln for discussions on XAS data collection and analysis.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/6/20
Y1 - 2019/6/20
N2 - The design, synthesis, and properties of a new gadolinium-based copper-responsive magnetic resonance imaging (MRI) contrast agent is presented. The sensor (GdL1) has high selectivity for copper ions and exhibits a 43% increase in r1 relaxivity (20 MHz) upon binding to 1 equiv of Cu2+ in aqueous buffer. Interestingly, in the presence of physiological levels of human serum albumin (HSA), the r1 relaxivity is amplified further up to 270%. Additional spectroscopic and X-ray absorption spectroscopy (XAS) studies show that Cu2+ is coordinated by two carboxylic acid groups and the single amine group on an appended side chain of GdL1 and forms a ternary complex with HSA (GdL1-Cu2+-HSA). T1-weighted in vivo imaging demonstrates that GdL1 can detect basal, endogenous labile copper(II) ions in living mice. This offers a unique opportunity to explore the role of copper ions in the development and progression of neurological diseases such as Wilson's disease.
AB - The design, synthesis, and properties of a new gadolinium-based copper-responsive magnetic resonance imaging (MRI) contrast agent is presented. The sensor (GdL1) has high selectivity for copper ions and exhibits a 43% increase in r1 relaxivity (20 MHz) upon binding to 1 equiv of Cu2+ in aqueous buffer. Interestingly, in the presence of physiological levels of human serum albumin (HSA), the r1 relaxivity is amplified further up to 270%. Additional spectroscopic and X-ray absorption spectroscopy (XAS) studies show that Cu2+ is coordinated by two carboxylic acid groups and the single amine group on an appended side chain of GdL1 and forms a ternary complex with HSA (GdL1-Cu2+-HSA). T1-weighted in vivo imaging demonstrates that GdL1 can detect basal, endogenous labile copper(II) ions in living mice. This offers a unique opportunity to explore the role of copper ions in the development and progression of neurological diseases such as Wilson's disease.
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U2 - 10.1021/jacs.8b13493
DO - 10.1021/jacs.8b13493
M3 - Article
C2 - 31268706
AN - SCOPUS:85070025021
SN - 0002-7863
VL - 141
SP - 11009
EP - 11018
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 28
ER -