Stability and Biodistribution of a Biodegradable Macromolecular MRI Contrast Agent Gd-DTPA Cystamine Copolymers (GDCC) in Rats
2010
Wu, Xueming | Zong, Yuda | Ye, Zhen | Lu, Zheng-Rong
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 ≈ 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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