Gd Complexes of DO3A-(Biphenyl-2,2′-bisamides) Conjugates as MRI Blood-Pool Contrast Agents

We report the synthesis of DO3A derivatives of 2,2'-diaminobiphenyl (1a,b) and their Gd complexes of the type [Gd(1)(H2O)]·xH2O (2a,b) for use as new MRI blood-pool contrast agents (BPCAs) that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of 2 compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. The R 1 relaxivity in water reaches 7.3 mM(-1) s(-1), which is approximately twice as high as that of Dotarem (R 1 = 3.9 mM(-1) s(-1)). They show interaction with HSA to give association constants (K a) in the order of two (∼10(2)), revealing the existence of the blood-pool effect. The in vivo MR images of mice obtained with 2 are coherent, showing strong signal enhancement in both heart, abdominal aorta, and small vessels. Furthermore, the brain tumor is vividly enhanced for an extended period of time.