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

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 (r₁ = 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.