Xueming Wu1, Yuda Zong, Zhen Ye, Zheng-Rong Lu. 1. Department of Biomedical Engineering, Case Western Reserve University, Wickenden Building, Room 427, 10900 Euclid Avenue, Cleveland, Ohio 44106-7207, USA.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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.
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