Mn(II) Complex of Lipophilic Group-Modified Ethylenediaminetetraacetic Acid (EDTA) as a New Hepatobiliary MRI Contrast Agent.

Abstract

Liver-specific contrast agents (CAs) can improve the Magnetic resonance imaging (MRI) detection of focal and diffuse liver lesions by increasing the lesion-to-liver contrast. A novel Mn(II) complex, Mn-BnO-TyrEDTA, with a lipophilic group-modified ethylenediaminetetraacetic acid (EDTA) structure as a ligand to regulate its behavior in vivo, is superior to Gd-EOB-DTPA in terms of a liver-specific MRI contrast agent. An MRI study on mice demonstrated that Mn-BnO-TyrEDTA can be rapidly taken up by hepatocytes with a combination of hepatobiliary and renal clearance pathways. Bromosulfophthalein (BSP) inhibition imaging, biodistribution, and cellular uptake studies confirmed that the mechanism of hepatic targeting of Mn-BnO-TyrEDTA is the hepatic uptake of the amphiphilic anion contrast agent mediated by organic anion transporting polypeptides (OATPs) expressed by functional hepatocytes.