PEGylated Amphiphilic Gd-DOTA Backboned-Bound Branched Polymers as Magnetic Resonance Imaging Contrast Agents.

MRI contrast agents with high kinetic stability and relaxivity are the key objectives in the field. We previously reported that Gd-DOTA backboned-bound branched polymers possess high kinetic stability and significantly increased T 1 relaxivity than traditional branched polymer contrast agents. In this work, non-PEGylated and PEGylated amphiphilic Gd-DOTA backboned-bound branched polymers [P(GdDOTA-C 6 ), P(GdDOTA-C 10 ), mPEG-P(GdDOTA-C 6 ), and mPEG-P(GdDOTA-C 10 )] were obtained by sequential introduction of rigid carbon chains (1,6-hexamethylenediamine or 1,10-diaminodecane) and mPEG into the structure of Gd-DOTA backboned-bound branched polymers. It is found that the introduction of both rigid carbon chains, especially the longer one, and mPEG can increase the kinetic stability and T 1 relaxivity of Gd-DOTA backboned-bound branched polymers. Among them, mPEG-P(GdDOTA-C 10 ) possesses the highest kinetic stability (significantly higher than those of linear Gd-DTPA and cyclic Gd-DOTA-butrol) and T 1 relaxivity (42.9 mM -1 s -1 , 1.5 T), 11 times that of Gd-DOTA and 1.4 times that of previously reported Gd-DOTA backboned-bound branched polymers. In addition, mPEG-P(GdDOTA-C 10 ) showed excellent MRA effect in cardiovascular and hepatic vessels at a dose (0.025 or 0.05 mmol Gd/kg BW) far below the clinical range (0.1-0.3 mmol Gd/kg BW). Overall, effective branched-polymer-based contrast agents can be obtained by a strategy in which rigid carbon chains and PEG were introduced into the structure of Gd-DOTA backbone-bound branched polymers, resulting in excellent kinetic stability and enhanced T 1 relaxivity.