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

• Published in: Angewandte Chemie Vol. 133; no. 19; pp. 10831 - 10839
• Main Authors: Anbu, Sellamuthu, Hoffmann, Sabrina H. L., Carniato, Fabio, Kenning, Lawrence, Price, Thomas W., Prior, Timothy J., Botta, Mauro, Martins, Andre F., Stasiuk, Graeme J.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 03-05-2021
• Subjects: bishydrated MnCA; Bladder; blood pool agents; Chemistry; Contrast agents; Contrast media; Gadolinium; Gadopentetate dimeglumine; In vivo methods and tests; in vivo MRI; Lability; Magnetic fields; Magnetic resonance imaging; Manganese; Mn-based contrast agents; Physicochemical properties; Renal function; template synthesis
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202100885

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, MnLMe, and studied the most important physicochemical properties in vitro. MnLMe displays optimized r1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r1b=21.1 mM−1 s−1 (20 MHz, 298 K, pH 7.4) upon binding to BSA (Ka=4.2×103 M−1). In vivo studies show that MnLMe is cleared intact into the bladder through renal excretion and has a prolonged blood half‐life compared to the commercial GdCA Magnevist. MnLMe shows great promise as a novel MRI contrast agent.
We present a single‐pot template synthesis strategy for a manganese‐based MRI contrast agent, MnLMe. MnLMe is highly inert toward zinc‐transmetallation and displays enhanced T1 relaxivity upon non‐covalent interaction with serum albumin. In vivo studies show higher contrast enhancement in the liver and longer blood half‐life than that of the commercially available contrast agent Magnevist. MnLMe shows great potential for use as a blood pool agent.