Highly Inert Gd-DOTA-Based Contrast Agents with a Lipophilic Side Chain for Hepatobiliary and Vascular Magnetic Resonance Imaging

Gadolinium (Gd3+) based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI) but are limited due to Gd3+ leakage risk and low sensitivity. Gd-DOTA enjoys the highest inertness and stability among the clinical GBCAs, and lipophilic 3-phenylpropylamine and 3,3-diphenylpropylamine were linked to Gd-DOTABA in this study, giving Gd-L1 and Gd-L2 for hepatobiliary and vascular MRI, respectively. Both complexes demonstrated superior inertness, with dissociation half-lives in 1 M HCl solution and at 37 °C measured to be around 4 times longer than that of Gd-DOTA. The hepatic MRI performance of Gd-L1 was comparable to commercial Gd-BOPTA as investigated in mice. The r1 of Gd-L2 in the presence of HSA was determined as high as 14.8 mM–1 s–1 (1.4 T and 37 °C), and its blood elimination half-life was determined at around 18 min in a rabbit model, thus making it an effective candidate for vascular MRI.