Pharmacokinetics and tissue retention of (Gd-DTPA)-cystamine copolymers, a biodegradable macromolecular magnetic resonance imaging contrast agent

Xinghe Wang, Yi Feng, Tianyi Ke, Matthias Schabel, Zheng Rong Lu

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Purpose. To investigate the pharmacokinetics, long-term tissue retention of Gd(III) ions, and magnetic resonance imaging (MRI) contrast enhancement of extracellular biodegradable macromolecular Gd(III) complexes, (Gd-DTPA)-cystamine copolymers (GDCC), of different molecular weights. Methods. The pharmacokinetics of blood clearance and long-term Gd(III) retention of GDCC were investigated in Sprague-Dawley rats. Pharmacokinetic parameters were calculated by using a two-compartment model. The blood pool contrast enhancement of GDCC was evaluated in Sprague-Dawley rats on a Siemens Trio 3T MR scanner. Gd-(DTPA-BMA) was used as a control. Results. The α phase half-life of Gd-(DTPA-BMA) and GDCC with molecular weights of 18,000 (GDCC-18) and 60,000 Da (GDCC-60) was 0.48 ± 0.16 min, 1.08 ± 0.24 min, and 1.74 ± 0.57 min, and the β phase half-life was 21.2 ± 5.5 min, 26.5 ± 5.9 min, and 53.7 ± 15.9 min, respectively. GDCC had minimal long-term Gd tissue retention comparable to that of Gd-(DTPA-BMA). GDCC resulted in more significant contrast enhancement in the blood pool than Gd-(DTPA-BMA). Conclusions. GDCC provides a prolonged blood pool retention time for effective MRI contrast enhancement and then clears rapidly with minimal accumulation of Gd (III) ions. It is promising for further development as a blood pool MRI contrast agent.

Original languageEnglish (US)
Pages (from-to)596-602
Number of pages7
JournalPharmaceutical Research
Volume22
Issue number4
DOIs
StatePublished - Apr 1 2005

Keywords

  • (Gd-DTPA)-cystamine copolymers
  • Biodegradable macromolecular contrast agent
  • Gd tissue accumulation
  • MRI
  • Pharmacokinetics

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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