Synthesis and Evaluation of Manganese(II)-Based Ethylenediaminetetraacetic Acid-Ethoxybenzyl Conjugate as a Highly Stable Hepatobiliary Magnetic Resonance Imaging Contrast Agent

In this study, we designed and synthesized a highly stable manganese (Mn²⁺)-based hepatobiliary complex by tethering an ethoxybenzyl (EOB) moiety with an ethylenediaminetetraacetic acid (EDTA) coordination cage as an alternative to the well-established hepatobiliary gadolinium (Gd³⁺) chelates and evaluated its usage as a T₁ hepatobiliary magnetic resonance imaging (MRI) contrast agent (CA). This new complex exhibits higher r₁ relaxivity (2.3 mM^-1 s^-1) than clinically approved Mn²⁺-based hepatobiliary complex Mn-DPDP (1.6 mM^-1 s^-1) at 1.5 T. Mn-EDTA-EOB shows much higher kinetic inertness than that of clinically approved Gd³⁺-based hepatobiliary MRI CAs, such as Gd-DTPA-EOB and Gd-BOPTA. In addition, in vivo biodistribution and MRI enhancement patterns of this new Mn²⁺ chelate are comparable to those of Gd³⁺-based hepatobiliary MRI CAs. The diagnostic efficacy of the new complex was demonstrated by its enhanced tumor detection sensitivity in a liver cancer model using in vivo MRI.