Gadolinium-based contrast agents built of DO3A-pyridine scaffold: Precisely tuning carboxylate group for enhanced magnetic resonance imaging

It is greatly desired to develop novel gadolinium-based contrast agents (GBCAs) as improved platforms for magnetic resonance imaging (MRI). Herein, we report the syntheses of a series of nonionic cyclenbased GBCAs by precisely tuning carboxylate group on DO3A-pyridine scaffold. [Gd-DO3A-4cp] is isolated which adopts an octadentate coordination mode with a free carboxylate group at 4-position of pyridine. It shows the r 1 relaxivity of 5.8 (mmol/L) -1 s -1 (3 T, 25 degrees C), which is 75% higher than 3.3 (mmol/L) -1 s -1 of the clinic used [Gd-DOTA]. The possible mechanisms behind the enhanced relaxivity are investigated and proposed by structure-property relationship studies. After validation of low cytotoxicity and considerable kinetic inertness, in-vivo studies are further examined, demonstrating its good MRI performance, biodistribution as well as the way of excretion.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.