Zhou Xinlan, Ruan Xinzhong, Li Xingjiang, Xu Weiyuan, Xiao Xinhui, Chen Aiyi, Ding Yinghui, Zhang Jilai, Mo Gengshen, Jian Yong, Wu Xinyang, Ye Fangfu, Wang Zhiqiang, Li Yi, Dai Lixiong
Key Laboratory of Theoretical Organic Chemistry and Function Molecule, Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China.
Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China.
Chem Biomed Imaging. 2025 Apr 1;3(6):387-397. doi: 10.1021/cbmi.5c00012. eCollection 2025 Jun 23.
Magnetic resonance imaging (MRI) is a critical tool in medical diagnostics, yet conventional MRI contrast agents (CAs) are often limited by their small-molecule nature, resulting in rapid clearance and low relaxivity. This study presents a chiral strategy for developing high-performance polymeric gadolinium-based CAs, PAA-EOB-GdA and PAA-EOB-GdB, tailored for enhanced vascular and tumor imaging. Notably, PAA-EOB-GdA, a chiral Gd-DOTA derivative integrated with sodium poly-(acrylic acid) (PAA), benefits from the optimized water exchange rate of chiral Gd-(III) complex and the polymer effect of PAA, exhibiting exceptionally high relaxivity ( = 37.87 mM s, 11.9-fold of clinical Gd-DOTA) and showed remarkable imaging efficacy in magnetic resonance angiography (MRA) with low-dose administration (0.05 mmol kg) and an extended imaging duration. Its performance in tumor imaging was also impressive, maintaining superior enhancement values compared to Gd-DOTA. These characteristics feature PAA-EOB-GdA as a promising candidate for clinical diagnosis in both vascular and tumor imaging applications.
磁共振成像（MRI）是医学诊断中的关键工具，但传统的MRI造影剂（CAs）往往因其小分子性质而受到限制，导致快速清除和低弛豫率。本研究提出了一种手性策略，用于开发高性能的基于钆的聚合物造影剂PAA-EOB-GdA和PAA-EOB-GdB，专为增强血管和肿瘤成像而设计。值得注意的是，PAA-EOB-GdA是一种与聚（丙烯酸）钠（PAA）整合的手性钆-多胺大环配合物衍生物，受益于手性钆（III）配合物优化的水交换速率和PAA的聚合物效应，表现出极高的弛豫率（ = 37.87 mM s，是临床用钆-多胺大环配合物的11.9倍），并在低剂量给药（0.05 mmol kg）和延长成像时间的磁共振血管造影（MRA）中显示出显著的成像效果。其在肿瘤成像中的表现也令人印象深刻，与钆-多胺大环配合物相比，保持了更高的增强值。这些特性使PAA-EOB-GdA成为血管和肿瘤成像应用临床诊断的有希望的候选者。
