Rational Design of Gd-DOTA-Type Contrast Agents for Hepatobiliary Magnetic Resonance Imaging
Weiyuan Xu, Yi Lü, Jiao Xu, Huaping Li, Rongfeng Lan, Ruonan Gao, Yinghui Ding, Xinjian Ye, Kun Shu, Fangfu Ye, Zhihan Yan, Lixiong Dai
Abstract
The safety risks of gadolinium (Gd 3+ )-based contrast agents (GBCAs) arise from their inevitable leakage of Gd 3+, and the pursuit of more stable GBCAs for magnetic resonance imaging (MRI) has drawn increasing attention. Yet, Gd-EOB-DTPA and Gd-BOPTA are the only two authorized GBCAs for liver diagnosis in spite of their weak stability. In this study, one of the pendent arms of the most inert commercial Gd-DOTA was decorated with phenyl moieties, in which obvious enhancements of both kinetic and thermodynamic stability were achieved. Gd-L 4 with a para-substituted OBn group was observed with ready hepatocellular uptake, with significant contrast provided in diagnosing orthotopic hepatocellular carcinoma, and its hepatobiliary secretion accounted for more than 50% of the injection dose in mice. In this study, Gd-L 4 was found with comparable performance in liver MRI diagnosis to that of commercial Gd-EOB-DTPA and was thus deemed as an ideal candidate for further clinical applications.