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http://dx.doi.org/10.13104/jksmrm.2013.17.4.259

Pharmacokinetics and Bio-distribution of New Gd-complexes of DTPA-bis (amide) (L3) in a Rat Model  

Yan, Gen (Department of Radiology, the Second Affiliated Hospital, Shantou University Medical College)
Wu, Renhua (Department of Radiology, the Second Affiliated Hospital, Shantou University Medical College)
Chang, Yongmin (Department of Radiology & Molecular Medicine, Kyungpook National University)
Kang, Duksik (Department of Radiology, Bogang Hospital)
Publication Information
Investigative Magnetic Resonance Imaging / v.17, no.4, 2013 , pp. 259-266 More about this Journal
Abstract
Purpose : To investigate the blood pharmacokinetics and bio-distribution of DTPA-bis-amide (L3) Gd(III) complexes. Materials and Methods: The pharmacokinetics and bio-distribution of Gd $(L3)(H_2O){\cdot}nH_2O$ were investigated in Sprague-Dawley rats after intravenous administration at a dose of 0.1 mmol Gd/kg. The Gd content in the blood, various tissues, and organs was determined by ICP-AES. Blood pharmacokinetic parameters were calculated using a two-compartment model. Results: The half-lives of ${\alpha}$ phase and ${\beta}$ phase Gd $(L3)(H_2O){\cdot}nH_2O$ were $2.286{\pm}0.11$ min and $146.1{\pm}7.5$ min, respectively. The bio-distribution properties reveal that the complex is mainly excreted by the renal pathway, and possibly excreted by the hepatobiliary route. The concentration ratio of Gd (III) was significantly higher in the liver and spleen than in other organs, and small amounts of Gd (III) ion were detected in the blood or other tissues of rats only after 7 days of intravenous administration. Conclusion: The MRI contrast agent Gd $(L3)(H_2O){\cdot}nH_2O$ provides prolonged blood pool retention in the circulation and then clears rapidly with minimal accumulation of Gd(III) ions. The synthesis of gadolinium complexes with well-balanced lipophilicity and hydrophilicity shows promise for their further development as blood pool MRI contrast agents.
Keywords
Pharmacokinetics; MRI contrast agent; DTPA-bis (amide) (L3); Magnetic resonance imaging (MRI);
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