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 (<b>1a</b>,<b>b</b>) and their Gd complexes of the type [Gd­(<b>1</b>)­(H₂O)]·<i>x</i>H₂O (<b>2a</b>,<b>b</b>) for use as new MRI blood-pool contrast agents (BPCAs) that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of <b>2</b> compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. The <i>R</i>₁ relaxivity in water reaches 7.3 mM^–1 s^–1, which is approximately twice as high as that of Dotarem (<i>R</i>₁ = 3.9 mM^–1 s^–1). They show interaction with HSA to give association constants (<i>K</i>_a) in the order of two (∼10²), revealing the existence of the blood-pool effect. The in vivo MR images of mice obtained with <b>2</b> 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

Gadolinium Complex of 1,4,7,10-Tetraazacyclo­dodecane-1,4,7-trisacetic Acid (DO3A)–Ethoxybenzyl (EOB) Conjugate as a New Macrocyclic Hepatobiliary MRI Contrast Agent

We report the synthesis of a macrocyclic Gd chelate based on a 1,4,7,10-tetraazacyclo­dodecane-1,4,7-trisacetic acid (DO3A) coordinationn cage bearing an ethoxybenzyl (EOB) moiety and discuss its use as a <i>T</i>₁ hepatobiliary magnetic resonance imaging (MRI) contrast agent. The new macrocyclic liver agent shows high chelation stability and high <i>r</i>₁ relaxivity compared with linear-type Gd chelates, which are the current clinically approved liver agents. Our macrocyclic, liver-specific Gd chelate was evaluated in vivo through biodistribution analysis and liver MRI, which demonstrated its high tumor detection sensitivity and suggested that the new Gd complex is a promising contrast agent for liver cancer imaging