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

다국어 초록 (Multilingual Abstract)

<P>In this study, we designed and synthesized a highly stable manganese (Mn<SUP>2+</SUP>)-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 (Gd<SUP>3+</SUP>) chelates and evaluated its usage as a <I>T</I><SUB>1</SUB> hepatobiliary magnetic resonance imaging (MRI) contrast agent (CA). This new complex exhibits higher <I>r</I><SUB>1</SUB> relaxivity (2.3 mM<SUP>-1</SUP> s<SUP>-1</SUP>) than clinically approved Mn<SUP>2+</SUP>-based hepatobiliary complex Mn-DPDP (1.6 mM<SUP>-1</SUP> s<SUP>-1</SUP>) at 1.5 T. Mn-EDTA-EOB shows much higher kinetic inertness than that of clinically approved Gd<SUP>3+</SUP>-based hepatobiliary MRI CAs, such as Gd-DTPA-EOB and Gd-BOPTA. In addition, in vivo biodistribution and MRI enhancement patterns of this new Mn<SUP>2+</SUP> chelate are comparable to those of Gd<SUP>3+</SUP>-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.</P>
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