Abstract

Chemical exchange saturation transfer (CEST) MRI has recently emerged as a versatile molecular imaging approach in which diamagnetic compounds can be utilized to generate an MRI signal. To expand the scope of CEST MRI applications, herein, we systematically investigated the CEST properties of N-aryl amides with different N-aromatic substitution, revealing their chemical shifts (4.6-5.8 ppm) and exchange rates (up to thousands s-1 ) are favorable to be used as CEST agents as compared to alkyl amides. As the first proof-of-concept study, we used CEST MRI to detect the enzymatic metabolism of the drug acebutolol directly by its intrinsic CEST signal without any chemical labeling. Our study implies that N-aryl amides may enable the label-free CEST MRI detection of the metabolism of many N-aryl amide-containing drugs and a variety of enzymes that act on N-aryl amides, greatly expanding the scope of CEST MR molecular imaging.

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