PEG-g-poly(GdDTPA-co-L-cystine): a biodegradable macromolecular blood pool contrast agent for MR imaging.
Biodegradable PEGylated Gd-DTPA l-cystine copolymers, PEG-g-poly(GdDTPA-co-l-cystine), were prepared and tested as a blood pool contrast agent in mice. The biodegradable macromolecular agent was designed to be broken down into smaller Gd complexes by endogenous thiols via the disulfide-thiol exchange reaction to facilitate the clearance of Gd complexes after the contrast-enhanced MRI examination. Gd-DTPA l-cystine copolymers were synthesized by condensation polymerization of l-cystine and DTPA-dianhydride in water followed by chelating with Gd(OAc)(3). MPEG-NH(2) (MW = 2000) was then conjugated to the polymeric backbone in different ratios. The macromolecular contrast agent was readily degraded with the incubation of l-cysteine. It also demonstrated superior contrast enhancement in the heart and blood vessels as compared to a low molecular weight control agent, Gd-(DTPA-BMA). At 1 h postcontrast, the PEGylated macromolecular agent still showed prominent enhancement, while little contrast enhancement was detectable in the blood pool by the control agent. PEG-g-poly(GdDTPA-co-l-cystine) shows promise as an MR blood pool imaging agent.
Mohs
Aaron M
AM
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Wang
Xinghe
X
Goodrich
K Craig
KC
Zong
Yuda
Y
Parker
Dennis L
DL
Lu
Zheng-Rong
ZR
D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism*; D003553:Cystine / Q000097:blood* / Q000737:chemistry; D019786:Gadolinium DTPA / Q000097:blood* / Q000737:chemistry; D046911:Macromolecular Substances / Q000097:blood / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*
D003287:Contrast Media; D046911:Macromolecular Substances; D011092:Polyethylene Glycols; D003553:Cystine; D019786:Gadolinium DTPA