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℃),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.