Dual-Site Chiral Engineering of a Fully Alkyl-Substituted Gd-DOTA Yields a High-Performance and Safe Hepatobiliary MRI Contrast Agent

Safety concerns associated with the release of a tiny amount of gadolinium (Gd³⁺) from clinically used gadolinium-based contrast agents (GBCAs) underscore the need for ultrastable alternatives for magnetic resonance imaging (MRI). Here we report Gd-L2, a fully alkyl-substituted, chiral Gd-DOTA derivative incorporating a tetraethyl-substituted cyclen backbone and α-arm methyl groups. This dual-site chiral design enhances both kinetic inertness and relaxivity, providing a structu