title: 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.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Materials Science and Engineering, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.forename: Yuda
authors.initials: Y
authors.lastname: Zong
authors.forename: Tianyi
authors.initials: T
authors.lastname: Ke
authors.forename: Eun-Kee
authors.initials: EK
authors.lastname: Jeong
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Parker
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D003553:Cystine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015637:Gated Blood-Pool Imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; C515817:gadolinium-DTPA cystine copolymer; C515818:gadolinium-DTPA cystine diethyl ester copolymer; D003553:Cystine; D004369:Pentetic Acid