TY - JOUR
T1 - Amplifying the Sensitivity of Zinc(II) Responsive MRI Contrast Agents by Altering Water Exchange Rates
AU - Yu, Jing
AU - Martins, André F.
AU - Preihs, Christian
AU - Clavijo Jordan, Veronica
AU - Chirayil, Sara
AU - Zhao, Piyu
AU - Wu, Yunkou
AU - Nasr, Khaled
AU - Kiefer, Garry E.
AU - Sherry, A. Dean
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/11/11
Y1 - 2015/11/11
N2 - Given the known water exchange rate limitations of a previously reported Zn(II)-sensitive MRI contrast agent, GdDOTA-diBPEN, new structural targets were rationally designed to increase the rate of water exchange to improve MRI detection sensitivity. These new sensors exhibit fine-tuned water exchange properties and, depending on the individual structure, demonstrate significantly improved longitudinal relaxivities (r1). Two sensors in particular demonstrate optimized parameters and, therefore, show exceptionally high longitudinal relaxivities of about 50 mM-1 s-1 upon binding to Zn(II) and human serum albumin (HSA). This value demonstrates a 3-fold increase in r1 compared to that displayed by the original sensor, GdDOTA-diBPEN. In addition, this study provides important insights into the interplay between structural modifications, water exchange rate, and kinetic stability properties of the sensors. The new high relaxivity agents were used to successfully image Zn(II) release from the mouse pancreas in vivo during glucose stimulated insulin secretion.
AB - Given the known water exchange rate limitations of a previously reported Zn(II)-sensitive MRI contrast agent, GdDOTA-diBPEN, new structural targets were rationally designed to increase the rate of water exchange to improve MRI detection sensitivity. These new sensors exhibit fine-tuned water exchange properties and, depending on the individual structure, demonstrate significantly improved longitudinal relaxivities (r1). Two sensors in particular demonstrate optimized parameters and, therefore, show exceptionally high longitudinal relaxivities of about 50 mM-1 s-1 upon binding to Zn(II) and human serum albumin (HSA). This value demonstrates a 3-fold increase in r1 compared to that displayed by the original sensor, GdDOTA-diBPEN. In addition, this study provides important insights into the interplay between structural modifications, water exchange rate, and kinetic stability properties of the sensors. The new high relaxivity agents were used to successfully image Zn(II) release from the mouse pancreas in vivo during glucose stimulated insulin secretion.
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U2 - 10.1021/jacs.5b09158
DO - 10.1021/jacs.5b09158
M3 - Article
C2 - 26462412
AN - SCOPUS:84947460644
SN - 0002-7863
VL - 137
SP - 14173
EP - 14179
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 44
ER -