Manganese-based contrast agents (MBCAs) are promising alternatives to currently used gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). This study describes the synthesis and physicochemical evaluation of two new zwitterionic Mn(III) porphyrin chelates (Mn-8 and Mn-9). Both compounds were synthesized via copper-catalyzed azide-alkyne cycloaddition (CuAAC) from an azido-substituted precursor. Both zwitterionic compounds are soluble in water and are remarkably stable to acidic pH and transmetallation under challenging conditions. The complexes have a high T1-relaxivity, comparable to current clinical high-relaxivity GBCAs like gadopiclenol. In addition, zwitterionic complexes Mn-8 and Mn-9 have superior relaxivity and improved stability compared to Mn-DPDP (mangafodipir, Teslascan). The favorable properties of both compounds can be attributed to the decoration of the chelator with sulfobetaines or N-oxides. Importantly, chelation of Mn(III) by the porphyrin drastically reduces singlet oxygen generation. Mn-8 showed good contrast enhancement in vivo. These compounds are thus strong candidates for the development of next-generation gadolinium-free MRI contrast agents.
Ludolfs et al. (2026) studied this question.