TY - JOUR
T1 - Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent
AU - MacRenaris, Keith W.
AU - Ma, Zhidong
AU - Krueger, Ruby L.
AU - Carney, Christiane E.
AU - Meade, Thomas J.
N1 - Funding Information:
This work was supported by the National Institutes of Health grants R01EB005866 and R01EB014806 as well as a CBC Spark Award S-003 and National Science Foundation Graduate Research Fellowship (C.E.C.). A portion of this work was completed at the Northwestern University Integrated Molecular Structure Education and Research Center. Imaging was performed at the Northwestern University Center for Advanced Molecular Imaging generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. MRI was performed on the 7 T Bruker Pharmscan system purchased with the support of NCRR 1S10RR025624-01. Metal analysis was performed at the Northwestern University Quantitative Bioelement Imaging Center generously supported by NASA Ames Research Center NNA06CB93G.
Publisher Copyright:
© 2015 American Chemical Society.
PY - 2016/2/17
Y1 - 2016/2/17
N2 - Calcium [Ca(II)] is a fundamental transducer of electrical activity in the central nervous system (CNS). Influx of Ca(II) into the cytosol is responsible for action potential initiation and propagation, and initiates interneuronal communication via release of neurotransmitters and activation of gene expression. Despite the importance of Ca(II) in physiology, it remains a challenge to visualize Ca(II) flux in the central nervous system (CNS) in vivo. To address these challenges, we have developed a new generation, Ca(II)-activated MRI contrast agent that utilizes ethyl esters to increase cell labeling and prevent extracellular divalent Ca(II) binding. Following labeling, the ethyl esters can be cleaved, thus allowing the agent to bind Ca(II), increasing relaxivity and resulting in enhanced positive MR image contrast. The ability of this probe to discriminate between extra- And intracellular Ca(II) may allow for spatiotemporal in vivo imaging of Ca(II) flux during seizures or ischemia where large Ca(II) fluxes (1-10 μM) can result in cell death.
AB - Calcium [Ca(II)] is a fundamental transducer of electrical activity in the central nervous system (CNS). Influx of Ca(II) into the cytosol is responsible for action potential initiation and propagation, and initiates interneuronal communication via release of neurotransmitters and activation of gene expression. Despite the importance of Ca(II) in physiology, it remains a challenge to visualize Ca(II) flux in the central nervous system (CNS) in vivo. To address these challenges, we have developed a new generation, Ca(II)-activated MRI contrast agent that utilizes ethyl esters to increase cell labeling and prevent extracellular divalent Ca(II) binding. Following labeling, the ethyl esters can be cleaved, thus allowing the agent to bind Ca(II), increasing relaxivity and resulting in enhanced positive MR image contrast. The ability of this probe to discriminate between extra- And intracellular Ca(II) may allow for spatiotemporal in vivo imaging of Ca(II) flux during seizures or ischemia where large Ca(II) fluxes (1-10 μM) can result in cell death.
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U2 - 10.1021/acs.bioconjchem.5b00561
DO - 10.1021/acs.bioconjchem.5b00561
M3 - Article
C2 - 26689452
AN - SCOPUS:84959371097
SN - 1043-1802
VL - 27
SP - 465
EP - 473
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 2
ER -