A Single-Pot Template Reaction Towards a Manganese-Based T₁ Contrast Agent

Manganese-based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium-based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single-pot template synthetic strategy to develop a MnCA, MnL^Me, and studied the most important physicochemical properties in vitro. MnL^Me displays optimized r₁ relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r₁^b=21.1 mM⁻¹ s⁻¹ (20 MHz, 298 K, pH 7.4) upon binding to BSA (K_a=4.2×10³ M⁻¹). In vivo studies show that MnL^Me is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCA Magnevist. MnL^Me shows great promise as a novel MRI contrast agent.