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N-Aryl Amides as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agents |
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| Authors: | Xuekang Cai Jia Zhang Jiaqi Lu Long Yi Zheng Han Shuixing Zhang Xing Yang Guanshu Liu |
| Affiliation: | 1. Department of Nuclear Medicine, Peking University First Hospital, 100034 Beijing, P. R. China State Key Laboratory of Organic-Inorganic Composites and Beijing Key Lab of Bioprocess, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Chaoyang District, 100029 Beijing, P. R. China Institute of Medical Technology, Peking University, 100871 Beijing, P. R. China These authors contributed equally to this work.;2. Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205 USA F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, 21205 USA These authors contributed equally to this work.;3. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, 21218 USA;4. State Key Laboratory of Organic-Inorganic Composites and Beijing Key Lab of Bioprocess, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Chaoyang District, 100029 Beijing, P. R. China Institute of Medical Technology, Peking University, 100871 Beijing, P. R. China;5. Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205 USA F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, 21205 USA;6. Department of Radiology, The First Affiliated Hospital of Jinan University, 510632 Guangzhou, Guandong, P. R. China;7. Department of Nuclear Medicine, Peking University First Hospital, 100034 Beijing, P. R. China;8. Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205 USA |
| 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. |
| Keywords: | acebutolol metabolism CEST MRI enzyme detection MRI contrast agent N-aryl amides |