Pharmaceutical Research

, Volume 23, Issue 8, pp 1736–1742 | Cite as

Pharmacokinetics, Biodistribution and Contrast Enhanced MR Blood Pool Imaging of Gd-DTPA Cystine Copolymers and Gd-DTPA Cystine Diethyl Ester Copolymers in a Rat Model

  • Yi Feng
  • Yuda Zong
  • Tianyi Ke
  • Eun-Kee Jeong
  • Dennis L. Parker
  • Zheng-Rong Lu
Research Paper


To investigate plasma pharmacokinetics and biodistribution of biodegradable polydisulfide Gd(III) complexes, Gd-DTPA cystine copolymers (GDCP) and Gd-DTPA cystine diethyl ester copolymers (GDCEP) and their efficacy as blood pool MRI contrast agents in comparison with a nondegradable macromolecular agent, Gd-DTPA 1,6-hexanediamine copolymers (GDHC).


The pharmacokinetics and biodistribution of GDCP and GDCEP with molecular weight of 35 KDa were investigated in Sprague‐Dawley rats after intravenous administration at a dose of 0.1 mmol Gd/kg. GDHC with the same molecular weight was used as a control. The Gd content in the plasma and various tissues and organs were determined by the ICP-OES. Plasma pharmacokinetic parameters were calculated by using a two-compartment model. The contrast enhanced blood pool MR imaging of the agents was evaluated in Sprague‐Dawley rats on a Siemens Trio 3T MR scanner.


The biodegradable macromolecular agents, GDCP and GDCEP, had faster blood pool clearance than the nondegradable GDHC. The long-term Gd(III) tissue retention of the biodegradable polydisulfide agents was substantially lower than the nondegradable macromolecular agent. Both GDCP and GDCEP resulted in significant blood pool enhancement for the first 2 min post-injection and more rapid disappearance of the enhancement over time than GDHC. The negatively charged GDCP had prolonged enhancement duration as compared to GDCEP. The structure and biodegradability of the macromolecular contrast agents significantly affected their pharmacokinetics and blood pool contrast enhancement.


Both GDCP and GDCEP provided effective contrast enhancement for MR imaging of the blood pool. The accumulation of toxic Gd(III) ions in the body was greatly reduced with GDCP and GDCEP as compared to the nondegradable control.

Key words

biodegradable Gd tissue accumulation MRI contrast agent pharmacokinetics polydisulfide Gd(III) complexes 



The research work is supported in part by the NIH grants R33 CA095873 and R01 EB00489. The authors thank Sheryl Dutson and Melody Johnson for technical support and valuable discussion.


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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Yi Feng
    • 1
  • Yuda Zong
    • 2
  • Tianyi Ke
    • 2
  • Eun-Kee Jeong
    • 3
  • Dennis L. Parker
    • 3
  • Zheng-Rong Lu
    • 2
    • 4
  1. 1.Department of Materials Science and EngineeringUniversity of UtahSalt Lake CityUSA
  2. 2.Department of Pharmaceutics and Pharmaceutical ChemistryUniversity of UtahSalt Lake CityUSA
  3. 3.Department of RadiologyUniversity of UtahSalt Lake CityUSA
  4. 4.Salt Lake CityUSA

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