Gadolinium-free Magnetic Resonance Imaging of the Liver via an Oatp1-Targeted Manganese(III) Porphyrin.

Controversy surrounding gadolinium-based contrast agents (GBCAs) has rendered their continued utility highly contentious, but the liver-specific GBCA Gd(III) ethoxybenzyl-diethylene triamine pentaacetic acid (Gd(III)-EOB-DTPA) remains in use because it provides unique diagnostic information that could not be obtained by any other means. To address the need for an alternate liver-specific MRI probe, we synthesized Mn(III) 20-(4-ethoxyphenyl) porphyrin-5,10,15-tricarboxylate (Mn(III)TriCP-PhOEt), which exhibited significantly higher relaxivity than Gd(III)-EOB-DTPA in vitro, while also targeting hepatocyte-specific organic anion-transporting polypeptide 1 (Oatp1) channels as a marker of viability. In mice, Mn(III)TriCP-PhOEt resulted in significant and specific increases in liver signal intensity on -weighted images and significant decreases in liver time relative to pre-contrast measurements. Our findings suggest that Mn(III)TriCP-PhOEt operates as a specific and sensitive MR probe for Oatp1-targeted imaging in vivo.