Gadolinium(III) Complex-Backboned Branched Polymers as Imaging Probes for Contrast-Enhanced Magnetic Resonance Angiography
Shengxiang Fu, Zhongyuan Cai, Li Liu, Xiaomin Fu, Changqiang Wu, Liang Du, Chunchao Xia, Su Lui, Qiyong Gong, Bin Song, Hua Ai
Abstract
Compared to traditional branched polymers with Gd(III) chelates conjugated on their surface, branched polymers with Gd(III) chelates as the internal skeleton are considered to be a reasonable strategy for preparing efficient magnetic resonance imaging contrast agents. Herein, the Gd(III) ligand DOTA was chosen as the internal skeleton; four different molecular weights (3.5, 5.3, 8.6, and 13.1 kDa) and degrees of branching poly-DOTA branched polymers (P1, P2, P3, and P4) were synthesized by a simple “A 2 + B 4 ”-type one-pot polymerization. The Gd(III) chelates of these poly-DOTA branched polymers (P1-Gd, P2-Gd, P3-Gd, and P4-Gd) display excellent kinetic stability, which is significantly higher than those of linear Gd-DTPA and cyclic Gd-DOTA-butrol and slightly lower than that of cyclic Gd-DOTA. The T 1 relaxivities of P1-Gd, P2-Gd, P3-Gd, and P4-Gd are 29.4, 38.7, 44.0, and 47.9 Gd mM –1 s –1, respectively, at 0.5 T, which are about 6–11 times higher than that of Gd-DOTA (4.4 Gd mM –1 s –1 ). P4-Gd was selected for in vivo magnetic resonance angiography (MRA) because of its high kinetic stability, T 1 relaxivity, and good biosafety. The results showed excellent MRA effect, sensitive detection of vascular stenosis, and prolonged observation window as compared to Gd-DOTA. Overall, Gd(III) chelates of poly-DOTA branched polymers are good candidates of MRI probes, providing a unique design strategy in which Gd chelation can occur at both the interior and surface of the poly-DOTA branched polymers, resulting in excellent relaxivity enhancement. In vivo animal MRA studies of the probe provide possibilities in discovering small vascular pathologies.