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

The
safety risks of gadolinium (Gd3+)-based
contrast
agents (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-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-L4 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-L4 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.