当前位置:
X-MOL 学术
›
J. Med. Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Rational Design of Mono-Substituted Gd-DOTA as Highly Stable and Efficient MRI Contrast Agents for Hepatobiliary and Inflammation Imaging
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-27 , DOI: 10.1021/acs.jmedchem.4c01084
Yinghui Ding 1, 2 , Xinzhong Ruan 3 , Kun Shu 4 , Weiyuan Xu 1 , Yao Liu 5 , Gengshen Mo 1 , Jiao Xu 1 , Yong Jian 1 , Jilai Zhang 2 , Lingfeng Zhang 4 , Keren Wang 4 , Ji-Ting Hou 6 , Jianliang Shen 6 , Zhihan Yan 4 , Fangfu Ye 1 , Jiang Zhu 5 , Lixiong Dai 1, 2
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-27 , DOI: 10.1021/acs.jmedchem.4c01084
Yinghui Ding 1, 2 , Xinzhong Ruan 3 , Kun Shu 4 , Weiyuan Xu 1 , Yao Liu 5 , Gengshen Mo 1 , Jiao Xu 1 , Yong Jian 1 , Jilai Zhang 2 , Lingfeng Zhang 4 , Keren Wang 4 , Ji-Ting Hou 6 , Jianliang Shen 6 , Zhihan Yan 4 , Fangfu Ye 1 , Jiang Zhu 5 , Lixiong Dai 1, 2
Affiliation
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.
中文翻译:
单取代 Gd-DOTA 作为高度稳定、高效的肝胆和炎症成像 MRI 造影剂的合理设计
肝胆特异性磁共振成像造影剂(MRI CA)在肝细胞癌(HCC)的早期诊断中发挥着至关重要的作用。然而,只有两种无环 CA,Gd-BOPTA 和 Gd-EOB-DTPA,表现出不利的动力学惰性。我们的研究重点是开发卓越稳定的创新大环CA。通过在 H 4 DOTA 环( Gd-L 1 )中引入亲脂性苄氧基(OBn),我们实现了动力学惰性的显着增强。小鼠体内实验表明,40%的剂量在5分钟内分布到肝脏,提供持续的肝脏增强超过35分钟。我们还开发了MPO响应性MRI CA( Gd-L 3 ),它可以作为底物参与“过氧化物酶循环”,生成弛豫率增加3.8倍的寡聚物,并选择性增强急性痛风小鼠的病灶模型。总体而言,我们的工作代表了肝脏和炎症 MRI 领域的重大进步,为早期诊断和改善成像结果提供了有希望的途径。
更新日期:2024-08-27
中文翻译:
单取代 Gd-DOTA 作为高度稳定、高效的肝胆和炎症成像 MRI 造影剂的合理设计
肝胆特异性磁共振成像造影剂(MRI CA)在肝细胞癌(HCC)的早期诊断中发挥着至关重要的作用。然而,只有两种无环 CA,Gd-BOPTA 和 Gd-EOB-DTPA,表现出不利的动力学惰性。我们的研究重点是开发卓越稳定的创新大环CA。通过在 H 4 DOTA 环( Gd-L 1 )中引入亲脂性苄氧基(OBn),我们实现了动力学惰性的显着增强。小鼠体内实验表明,40%的剂量在5分钟内分布到肝脏,提供持续的肝脏增强超过35分钟。我们还开发了MPO响应性MRI CA( Gd-L 3 ),它可以作为底物参与“过氧化物酶循环”,生成弛豫率增加3.8倍的寡聚物,并选择性增强急性痛风小鼠的病灶模型。总体而言,我们的工作代表了肝脏和炎症 MRI 领域的重大进步,为早期诊断和改善成像结果提供了有希望的途径。