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Lipophilic Group-Modified Manganese(II)-Based Contrast Agents for Vascular and Hepatobiliary Magnetic Resonance Imaging

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机构： [1]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China. [2]College of Biomedical Engineering, Sichuan University, Chengdu 610065, China. [3]Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China. [4]Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu 610065, China. [5]Sichuan Key Laboratory of Medical Imaging, North Sichuan Medical College, Nanchong 637000, China. [6]Nanchong Key Laboratory of MRI Contrast Agent, North Sichuan Medical College, Nanchong 637000, China. [7]Department of Nuclear Medicine, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China. [8]Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, China. [9]Psychoradiology Research Unit of Chinese Academy of Medical Sciences, Sichuan University, Chengdu 610041, China.

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Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.

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大类 | 1 区

医学

小类 | 1 区药物化学

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无

最新[2023]版：

Q1 CHEMISTRY, MEDICINAL

影响因子： 6.9 最新[2023版] 7.2 最新五年平均 6.9 出版当年[2023版] 0 出版当年五年平均 6.9 出版前一年[2023版]

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第一作者机构： [1]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China. [2]College of Biomedical Engineering, Sichuan University, Chengdu 610065, China.

通讯作者：

通讯机构： [1]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China. [2]College of Biomedical Engineering, Sichuan University, Chengdu 610065, China. [3]Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China.

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