Chiral Strategy for Developing High-Performance Polymeric Gadolinium-Based MRI Contrast Agents for Vascular and Tumor Imaging

Xinlan Zhou; Xinzhong Ruan; Xingjiang Li; Weiyuan Xu; Xinhui Xiao; Aiyi Chen; Yinghui Ding; Jilai Zhang; Gengshen Mo; Yong Jian; Xinyang Wu; Fangfu Ye; Zhiqiang Wang; Yi Li; Lixiong Dai

doi:10.1021/cbmi.5c00012

Chiral Strategy for Developing High-Performance Polymeric Gadolinium-Based MRI Contrast Agents for Vascular and Tumor Imaging

Chem Biomed Imaging. 2025 Apr 1;3(6):387-397. doi: 10.1021/cbmi.5c00012. eCollection 2025 Jun 23.

Authors

Xinlan Zhou^{1

2}, Xinzhong Ruan³, Xingjiang Li⁴, Weiyuan Xu², Xinhui Xiao², Aiyi Chen², Yinghui Ding², Jilai Zhang², Gengshen Mo², Yong Jian², Xinyang Wu⁵, Fangfu Ye², Zhiqiang Wang⁴, Yi Li¹, Lixiong Dai²

Affiliations

¹ 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.
² Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China.
³ Department of Radiology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China.
⁴ Department of Radiology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang 325000, China.
⁵ MR Philips (China) Investment Co. Ltd., Building A1, No. 718 Lingshi Road, Jing'an District, Shanghai 200072, China.

Abstract

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 (r ₁ = 37.87 mM^-1 s^-1, 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^-1) 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.

Keywords: Chiral Gadolinium Complex; Extended Imaging Duration; High Relaxivity; Polymeric MRI Contrast Agents; Vascular and Tumor Imaging.