Gd3+ Complexes with Slowly Exchanging Bound-Water Molecules May Offer Advantages in the Design of Responsive MR Agents

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Abstract
Zhang S, Wu K, Sherry AD. Gd3+ complexes with slowly exchanging bound-water molecules may offer advantages in the design of responsive MR agents. Invest Radiol 2001;36:82–86. Slow water exchange in Gd3+ complexes is generally considered detrimental to their use as MR contrast agents. The objective of this work was to demonstrate how this feature may serve as a useful template for the design of responsive MR agents. Lanthanide (Ln) complexes of two 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)–tetraamide phosphonate (1) and phosphonate ester (2) ligands were studied by multinuclear (1H, 13C, 31P, and 17O) nuclear MR spectroscopy. The inner-sphere water lifetime in the Ln(2) complexes was much longer (τM 298 = 0.8–1.3 ms) than in the corresponding Ln(1) complexes. This allowed direct detection of the bound-water molecule in europium(2) in water at 40° C by 1H nuclear MR. The water relaxivity of gadolinium(2) was independent of pH between 8.5 and 6.0, whereas the relaxivity of gadolinium(1) increased more than twofold in this pH range. T1-weighted images of phantoms containing gadolinium(1) at different pH values demonstrate the efficacy of this complex as a pH-sensitive MR contrast agent.