Synthesis and Relaxivity of One Macrocyclic Binuclear Nonionic Magnetic Resonance Contrast Agent

Abstract

Magnetic resonance imaging (MRI) is widely employed in diagnostic medicine and soft tissue imaging. Contrast agents (CAs) can improve the specificity of enhanced MRI images. Herein, the design, synthesis and relaxivity of a novel binuclear nonionic Gd-based DOTA-hydrazide (DOTA=1, 4, 7, 10-tetraazacyclododecan-1, 4, 7, 10-tetraacetic acid) derived MRI contrast agents, (Gd-DOTAH)2-SBDC, were reported. The improved longitudinal relaxivity was determined as 10.6 L•mmol-1•s-1 per molecule or 5.3 L•mmol-1•Gd-1•s-1 at 0.5 T, which is higher than that of the mononuclear clinical macrocyclic agent Gd-DOTA. In vitro MRI studies confirmed its suitability for use as a MRI contrast agent with improved diagnostic sensitivity and accuracy. Furthermore, the stilbene moiety endows it with myelin-targeting capabilities. In addition, two synthetic routes (A and B) for this contrast agent were compared, providing overall yields of 70% and 75%, respectivily, and route B was deemed superior.