Gd Complexes of DO3A-(Biphenyl-2,2′-bisamides)
Conjugates as MRI Blood-Pool Contrast Agents
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Abstract
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>)(H<sub>2</sub>O)]·<i>x</i>H<sub>2</sub>O (<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><sub>1</sub> relaxivity in
water reaches 7.3 mM<sup>–1</sup> s<sup>–1</sup>, which
is approximately twice as high as that of Dotarem (<i>R</i><sub>1</sub> = 3.9 mM<sup>–1</sup> s<sup>–1</sup>).
They show interaction with HSA to give association constants (<i>K</i><sub>a</sub>) in the order of two (∼10<sup>2</sup>), 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