Gd Complexes of DO3A-(Biphenyl-22′-bisamides)Conjugates as MRI Blood-Pool Contrast Agents

摘要

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 R1 relaxivity in water reaches 7.3 mM^–1 s^–1, which is approximately twice as high as that of Dotarem (R1 = 3.9 mM^–1 s^–1). They show interaction with HSA to give association constants (Ka) in the order of two (∼10²), 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.