Rational Design of Gd-DOTA-Type Contrast Agents for Hepatobiliary Magnetic Resonance Imaging

Thesafety risks of gadolinium (Gd3+)-basedcontrastagents (GBCAs) arise from their inevitable leakage of Gd3+, and the pursuit of more stable GBCAs for magnetic resonance imaging(MRI) has drawn increasing attention. Yet, Gd-EOB-DTPA and Gd-BOPTAare the only two authorized GBCAs for liver diagnosis in spite oftheir weak stability. In this study, one of the pendent arms of themost inert commercial Gd-DOTA was decorated with phenyl moieties,in which obvious enhancements of both kinetic and thermodynamic stabilitywere achieved. Gd-L ( 4 ) with a para-substitutedOBn group was observed with ready hepatocellular uptake, with significantcontrast provided in diagnosing orthotopic hepatocellular carcinoma,and its hepatobiliary secretion accounted for more than 50% of theinjection dose in mice. In this study, Gd-L ( 4 ) was found with comparable performance in liver MRIdiagnosis to that of commercial Gd-EOB-DTPA and was thus deemed asan ideal candidate for further clinical applications.