PEG-g-poly(GdDTPA-co-L-cystine): A biodegradable macromolecular blood pool contrast agent for MR imaging

Aaron M. Mohs, Xinghe Wang, K. Craig Goodrich, Yuda Zong, Dennis L. Parker, Zheng Rong Lu

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1424-1430
Number of pages7
JournalBioconjugate Chemistry
Volume15
Issue number6
DOIs
StatePublished - Nov 2004

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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