PEGylated amphiphilic polymeric manganese(II) complexes as magnetic resonance angiographic agents.

Currently, the most commonly used clinical magnetic resonance imaging (MRI) contrast agents, Gd(III) chelates, have been found to be associated with nephrogenic systemic fibrosis (NSF) in renally compromised patients. Toxicity concerns related to Gd(III)-based agents prompted intensive research toward the development of safe, efficient, and long-cycle non-Gd contrast agents. Herein, three amphiphilic polymeric manganese (Mn) ligands (mPEG-P(L-a-HMDI)-mPEG, mPEG-P(L-a-HMDI)-mPEG and mPEG-P(L-a-HMDI)-mPEG) were synthesized, and then end-capped respectively with different molecular weights of polyethylene glycol monomethyl ether (mPEG 1 kD, 2 kD and 4 kD) to obtain amphiphilic polymer Mn ligands. After being chelated with Mn(II), these amphiphilic polymer Mn complexes show significantly higher relaxivity than the small molecule Mn complex (MnL) at 0.5 T, 1.5 T and 3.0 T magnetic fields, respectively. Then, mPEG-P(MnL-a-HMDI)-mPEG with relatively high relaxivities (23.2, 14.4 and 9.7 mMs at 0.5 T, 1.5 T and 3.0 T, respectively), low CMC (4.7 mg L), reasonable size (48 nm) and excellent stability among these three polymer Mn complexes was selected for MR imaging of vascular vessels. The results suggest that mPEG-P(MnL-a-HMDI)-mPEG has an excellent and relatively long time-window vascular enhancement effect even at a low dose of 0.05 mmol Mn kg BW, and could play a role in the diagnosis of vascular diseases (0.1 mmol Mn kg BW). Therefore, mPEG-P(MnL-a-HMDI)-mPEG may be considered as a potential blood pool contrast agent.