title: PEGylated polyethylenimine as enhanced T₁ contrast agent for efficient magnetic resonance imaging.
abstract: Currently used small molecular magnetic resonance (MR) imaging contrast agents (CAs) in clinics have relatively short half-lives, which has limited the acquisition of high-resolution organ and angiographic images. Therefore, development of a facile strategy for the synthesis of long-circulating CAs with the transforming potential for MR imaging still remains a great challenge. Here we communicate the design and synthesis of PEGylated polyethylenimine (PEI) and its application as enhanced T1 CA for the long-circulating blood pool as well as efficient organ and tumor imaging. In this study, PEI was covalently grafted with gadolinium (Gd(III)) chelator and mPEG-NHS, followed by acetylation of the remaining amines to improve biocompatibility and prolong circulation time. With the relatively long circulation time (3.8 h), the formed multifunctional PEI (PEI.NHAc-DTPA(Gd(III))-mPEG) can be used as an enhanced T1 CA for blood pool and major organ imaging, and could be cleared from the body 96 h post administration through the urinary system. Importantly, the PEI.NHAc-DTPA(Gd(III))-mPEG complexes displayed a strong T1 contrast effect for tumor imaging through the enhanced permeation and retention effect. These findings suggest that the synthesized PEI.NHAc-DTPA(Gd(III))-mPEG may be used as a promising CA for T1 MR imaging of various biological systems.
authors.affiliation: Department of Orthopedics, Changzheng Hospital, Second Military Medical University , Shanghai 200003, People's Republic of China.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Zhou
authors.forename: Zhenkai
authors.initials: Z
authors.lastname: Wu
authors.forename: Xiongsheng
authors.initials: X
authors.lastname: Chen
authors.forename: Lianshun
authors.initials: L
authors.lastname: Jia
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002460:Cell Line; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003287:Contrast Media; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D005682:Gadolinium