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-NH2 (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.