title: Stability and biodistribution of a biodegradable macromolecular MRI contrast agent Gd-DTPA cystamine copolymers (GDCC) in rats.
abstract: OBJECTIVE
  The aim of this study was to evaluate stability and Gd tissue distribution of a biodegradable macromolecular MRI contrast agent, GDCC.
  
  
  METHODS
  Kinetic stability of GDCC was evaluated based on transmetallation with endogenous metal ions Zn2+ and Cu2+ in rat plasma in comparison with Omniscan, MultiHance and ProHance. In vivo transmetallation of GDCC was evaluated by determining metal content in the urine samples of Spague-Dawley rats. The biodistribution of the agents was determined in rats at 48 h post-injection.
  
  
  RESULTS
  A new method of using ultrafiltration was developed for study of kinetic stability against transmetallation of Gd(III)-based MRI contrast agents. Both in vitro and in vivo stability of the contrast agents towards transmetallation with Zn2+ were in the order of ProHance > MultiHance approximately GDCC > Omniscan. No significant transmetallation with Cu2+ was observed for the contrast agents. GDCC had comparable retention to the control agents in most organs and tissues with slightly high retention in the liver and kidneys at 48 h post-injection.
  
  
  CONCLUSIONS
  Ultrafiltration is efficient and accurate for characterizing the kinetic stability of Gd(III)-based MRI contrast agents. The novel biodegradable macromolecular contrast agent GDCC is promising for further development for contrast enhanced MRI.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Wickenden Building, Room 427, 10900 Euclid Avenue, Cleveland, Ohio 44106-7207, USA.
authors.forename: Xueming
authors.initials: X
authors.lastname: Wu
authors.forename: Yuda
authors.initials: Y
authors.lastname: Zong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ye
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
mesh_terms: D000818:Animals; D001682:Biological Availability; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D003538:Cystamine / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D019786:Gadolinium DTPA / Q000737:chemistry* / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D019786:Gadolinium DTPA; D003538:Cystamine
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