Amplifying the Sensitivity of Zinc(II) Responsive MRI Contrast Agents by Altering Water Exchange Rates

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• 作者：Jing Yu ; Andr茅 F. Martins ; Christian Preihs ; Veronica Clavijo Jordan ; Sara Chirayil ; Piyu Zhao ; Yunkou Wu ; Khaled Nasr ; Garry E. Kiefer ; A. Dean Sherry
• 刊名：Journal of the American Chemical Society
• 出版年：2015
• 出版时间：November 11, 2015
• 年：2015
• 卷：137
• 期：44
• 页码：14173-14179
• 全文大小：418K
• ISSN：1520-5126

文摘

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^鈥? s^鈥? 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.