The degradation and clearance of Poly(N-hydroxypropyl-l-glutamine)-DTPA-Gd as a blood pool MRI contrast agent

Guodong Zhang, Rui Zhang, Marites P. Melancon, Kelvin Wong, Jian You, Qian Huang, James Bankson, Dong Liang, Chun Li

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Although polymeric magnetic resonance imaging (MRI) agents have significantly improved relaxivity and prolonged circulation time in vivo compared with current imaging agents, the potential for long-term toxicity prevents their translation into the clinic. The aim of this study was to develop a new biodegradable, nonionic polymeric blood pool MRI contrast agent with efficient clearance from the body. We synthesized PHPG-DTPA, which possesses two potentially degradable sites in vivo: protein amide bonds of the polymer backbone susceptible to enzymatic degradation and hydrolytically labile ester bonds in the side chains. After chelation with Gd 3+, PHPG-DTPA-Gd displayed an R 1 relaxivity of 15.72 mm -1{dot operator}sec -1 (3.7 times higher than that of Magnevist T). In vitro, DTPA was completely released from PHPG polymer within 48 h when incubated in mouse plasma. In vivo, PHPG-DTPA-Gd was cleared via renal route as shown by micro-single photon emission computed tomography of mice after intravenous injection of 111In-labeled PHPG-DTPA-Gd. MRI of nude rats bearing C6 glioblastoma showed significant enhancement of the tumor periphery after intravenous injection of PHPG-DTPA-Gd. Furthermore, mouse brain angiography was clearly delineated up to 2 h after injection of PHPG-DTPA-Gd. PHPG-DTPA-Gd's biodegradability, efficient clearance, and significantly increased relaxivity make it a promising polymeric blood pool MRI contrast agent.

Original languageEnglish (US)
Pages (from-to)5376-5383
Number of pages8
JournalBiomaterials
Volume33
Issue number21
DOIs
StatePublished - Jul 2012

Keywords

  • Biodegradable
  • Blood pool imaging
  • Magnetic resonance imaging
  • Polymeric gadolinium chelates

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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