J Korean Soc Magn Reson Med.  2013 Dec;17(4):259-266. 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 G
• Wu R
• Chang Y
• Kang D

• KMID: 2144327
• DOI: http://doi.org/10.13104/jksmrm.2013.17.4.259

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)(H2O).nH2O 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 alphaphase and betaphase Gd (L3)(H2O).nH2O were 2.286+/-0.11 min and 146.1+/-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)(H2O).nH2O 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.

Keyword

Pharmacokinetics; MRI contrast agent; DTPA-bis (amide) (L3); Magnetic resonance imaging (MRI)

MeSH Terms

Administration, Intravenous
Animals
Contrast Media
Gadolinium
Hydrophobic and Hydrophilic Interactions
Ions
Liver
Magnetic Resonance Imaging
Models, Animal*
Pharmacokinetics*
Rats*
Rats, Sprague-Dawley
Spleen
Contrast Media
Gadolinium
Ions

Figure

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  Fig. 1 Scheme of Gd(L3)(H2O).nH2O.

• 

  Fig. 2 a. Blood concentration-time curves of Gd in rats exposed to Gd (L3)(H2O).nH2O. Data are presented as absolute values of plasma concentration and percentages of IV dose. b. Schematic presentation of pharmacokinetic indices in Gd (L3)(H2O).nH2O. Mean plasma concentration-time profiles of Gd.

• 

  Fig. 3 Time course of distribution of Gd to tissues at various times after the last injection of the L3. Error bars are average deviations of values for pairs of rats.

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  Fig. 4 Bio-distribution of gadolinium in rats 15 min after intravenous injection of Gd(L3)(H2O).nH2O at a dose of 0.1 mmol Gd/kg. Data presented as mean ± SD.

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  Fig. 5 The relaxation time (T1) maps and corresponding relaxivity (R1) maps on Gd(L3)(H2O).nH2O with various concentration of HSA. The bright signal intensity on the map means longer relaxation time. For relaxivity map, the bright signal intensity on the map represents higher relaxivity.

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