Rational Design of Gd-DOTA-Type Contrast Agents for Hepatobiliary Magnetic Resonance Imaging

被引：16

作者：

Xu, Weiyuan ^{[1
]}

Lu, Yi ^{[2
,3
]}

Xu, Jiao ^{[1
]}

Li, Huaping ^{[1
]}

Lan, Rongfeng ^{[4
]}

Gao, Ruonan ^{[1
]}

Ding, Yinghui ^{[1
]}

Ye, Xinjian ^{[2
,3
]}

Shu, Kun ^{[2
,3
]}

Ye, Fangfu ^{[5
,6
]}

Yan, Zhihan ^{[2
,3
]}

Dai, Lixiong ^{[1
,5
,7
]}

机构：

[1] Univ Chinese Acad Sci, Wenzhou Inst, Wenzhou Key Lab Biophys, Wenzhou 325000, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Affiliated Hosp 2, Dept Radiol, Wenzhou 325027, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China

[4] Shenzhen Univ, Sch Basic Med Sci, Dept Cell Biol & Med Genet, Hlth Sci Ctr, Shenzhen 518060, Guangdong, Peoples R China

[5] Wenzhou Med Univ, Joint Ctr Translat Med, Affiliated Hosp 1, Wenzhou 325035, Peoples R China

[6] Chinese Acad Sci, Inst Phys, Beijing Natl Lab Condensed Matter Phys, Beijing 100190, Peoples R China

[7] Wenzhou Med Univ, Zhejiang Engn Res Ctr Innovat & Applicat Intellige, Affiliated Hosp 2, Wenzhou 325000, Zhejiang, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 66卷 / 13期

基金：

中国国家自然科学基金;

关键词：

LANTHANIDE(III) COMPLEXES; HEPATIC KINETICS; HUMAN SERUM; GADOLINIUM; MRI; STABILITY; LIVER; ACID; DTPA; VISUALIZATION;

D O I：

10.1021/acs.jmedchem.3c00579

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Thesafety risks of gadolinium (Gd3+)-basedcontrastagents (GBCAs) arise from their inevitable leakage of Gd3+, and the pursuit of more stable GBCAs for magnetic resonance imaging(MRI) has drawn increasing attention. Yet, Gd-EOB-DTPA and Gd-BOPTAare the only two authorized GBCAs for liver diagnosis in spite oftheir weak stability. In this study, one of the pendent arms of themost inert commercial Gd-DOTA was decorated with phenyl moieties,in which obvious enhancements of both kinetic and thermodynamic stabilitywere achieved. Gd-L ( 4 ) with a para-substitutedOBn group was observed with ready hepatocellular uptake, with significantcontrast provided in diagnosing orthotopic hepatocellular carcinoma,and its hepatobiliary secretion accounted for more than 50% of theinjection dose in mice. In this study, Gd-L ( 4 ) was found with comparable performance in liver MRIdiagnosis to that of commercial Gd-EOB-DTPA and was thus deemed asan ideal candidate for further clinical applications.

引用

页码：8993 / 9005

页数：13

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