Gadolinium Complex of 1,4,7,10-Tetraazacyclododecane-N,N′,N″, N'''-1,4,7-trisacetic Acid (DO3A) Conjugate of Tranexamates: A Quest for a Liver-specific Magnetic Resonance Imaging Contrast Agent

The work is directed toward the synthesis of a series of DO3A conjugates of tranexamates (1c-e) and their Gd complexes (2c-e) for use as a liver-specific MRI CA. All these complexes show thermodynamic and kinetic stabilities comparable to those of structurally related clinical agents such as DotaremR. Their R1 relaxivities also compare well with those of commercial agent, ranging 3.68-4.84 mM^-1s^-1. In vivo MR images of mice with 2ae reveal that only 2a exhibits liver-specificity. Although 2b and 2c show strong enhancement in liver, yet no bile-excretion is observed to be termed as a liver-specific agent. The rest behaves much like ordinary ECF CAs like DotaremR. The new series possess no toxicity to be employed in vivo.