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 journalArticlepeer-review

19 Scopus citations


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
Issue number21
StatePublished - Jul 2012


  • 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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