机构：[1]Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China.[2]Postgraduate Training Base Alliance, Wenzhou Medical University, Wenzhou, Zhejiang 325001, China.[3]Department of Radiology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China.[4]Wenzhou Key Laboratory of the Structural and Functional Imaging, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.[5]Sichuan Key Laboratory of Medical Imaging, School of Basic Medical Sciences and Forensic Medicine and Nanchong Key Laboratory of MRI Contrast Agent, North Sichuan Medical College, Nanchong, Sichuan 637000, China.[6]National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Hepatobiliary-specific magnetic resonance imaging contrast agents (MRI CAs) play a crucial role in the early diagnosis of hepatocellular carcinoma (HCC). However, only two acyclic CAs, Gd-BOPTA and Gd-EOB-DTPA, exhibit unfavorable kinetic inertness. Our study focused on the development of superior stable innovative macrocyclic CAs. By introducing a lipophilic benzyloxy group (OBn) into the H4DOTA ring (Gd-L1), we achieved significant enhancement in kinetic inertness. In vivo experiments in mice demonstrated that 40% of the dosage was distributed to the liver at 5 min, providing sustained hepatic enhancement for over 35 min. We also developed an MPO-responsive MRI CA (Gd-L3), which can participate in the "peroxidase cycle" as the substrate, generating oligomers with a 3.8-fold increase in relaxivity, and selectively enhance the lesion in an acute gout mouse model. Overall, our work represents a significant advancement in the field of hepatic and inflammatory MRI, offering promising avenues for early diagnosis and improved imaging outcomes.
基金：
This work was financially supported by the National Natural
Science Foundation of China (22075281 and 22105201),
Zhenjiang Provincial Natural Science Foundation of China
(LZ21B010001), University of Chinese Academy of Science
(WIUCASQD2020008), and Wenzhou High-Level Innovation
Team (Development and application team of functional liver
cancer-on-a-chip).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2024]版：
无
最新[2023]版：
大类|1 区医学
小类|1 区药物化学
第一作者：
第一作者机构：[1]Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China.[2]Postgraduate Training Base Alliance, Wenzhou Medical University, Wenzhou, Zhejiang 325001, China.
共同第一作者：
通讯作者：
通讯机构：[1]Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China.[2]Postgraduate Training Base Alliance, Wenzhou Medical University, Wenzhou, Zhejiang 325001, China.
推荐引用方式(GB/T 7714)：
Ding Yinghui,Ruan Xinzhong,Shu Kun,et al.Rational Design of Mono-Substituted Gd-DOTA as Highly Stable and Efficient MRI Contrast Agents for Hepatobiliary and Inflammation Imaging[J].Journal Of Medicinal Chemistry.2024,67(17):15476-15493.doi:10.1021/acs.jmedchem.4c01084.
APA：
Ding Yinghui,Ruan Xinzhong,Shu Kun,Xu Weiyuan,Liu Yao...&Dai Lixiong.(2024).Rational Design of Mono-Substituted Gd-DOTA as Highly Stable and Efficient MRI Contrast Agents for Hepatobiliary and Inflammation Imaging.Journal Of Medicinal Chemistry,67,(17)
MLA：
Ding Yinghui,et al."Rational Design of Mono-Substituted Gd-DOTA as Highly Stable and Efficient MRI Contrast Agents for Hepatobiliary and Inflammation Imaging".Journal Of Medicinal Chemistry 67..17(2024):15476-15493
医学