[en] magnetic resonance imaging; [en] pharmacokinetics; [en] MRI contrast agents
Abstract :
[en] A new low-molecular weight dendrimer-like M RI contrast agent (Gd-D1) has been synthesized and characterized in vitro by proton and oxygen-17 relaxometry. Its pharmacokinetic parameters and biodistribution patterns were evaluated on rats. Its in vitro and in vivo properties, that is, the longitudinal relaxivity (defined as the increase of the water proton longitudinal relaxation rate induced by one millimole per liter of Gd-D1) equal to 5.6 s(-1) mM(-1) at 20 MHz and 310 K, the elimination half-time equal to 85 min, and its low accumulation in liver and spleen, underline its potential as a blood-pool MRI contrast agent.
Disciplines :
Pharmacy, pharmacology & toxicology Radiology, nuclear medicine & imaging Chemistry
Author, co-author :
Yu, G.
Yamashita, M.
Aoshima, Kengo
Takahashi, M.
Oshikawa, T.
Takayanagi, H.
Laurent, Sophie ; Université de Mons > Faculté de Médecine et de Pharmacie > Chimie générale, organique et biomédicale
Burtea, Carmen ; Université de Mons > Faculté de Médecine et de Pharmacie > Chimie générale, organique et biomédicale
Vander Elst, Luce ; Université de Mons > Faculté de Médecine et de Pharmacie > Biochimie métabolique et moléculaire
Muller, Robert ; Université de Mons > Faculté de Médecine et de Pharmacie > Chimie générale, organique et biomédicale
Language :
English
Title :
A glycosylated complex of gadolinium, a new potential contrast agent for magnetic resonance angiography?
Wang S.J., Brechbiel M., and Wiener E.C. Invest. Radiol. 38 10 (2003) 662
Takahashi M., Hara Y., Aoshima K., Kurihara H., Oshikawa T., and Yamashita M. Tetrahedron Lett. 41 (2000) 8485 (A solution of d-(+)-Glucono-1,5-lactone (7.05 g) in 45 mL of DMF was added to diethylenetriamine (2.04 g). The mixture was stirred for 5 h at room temperature and then was left in the refrigerator overnight. (Boc)2O (2.01 g) was added to the solution (4.23 g) at 0 °C and stirred overnight at room temperature. The mixture was added to Et3N (10.0 g) and Ac2O (9.40 g) at 0 °C, and then stirred for 2 days at room temperature. After the completion of the reaction, work-up gave a brown crystal. Trifluoroacetic acid (6.40 g) was added to the solution of the crystal (8.42 g) in CH2Cl2 (5 mL) and the mixture was allowed to react for 2 h at room temperature. After the completion of the reaction, work-up and the product isolation by recycle GPC gave diethylenetriamine bisgluconate (yield 74%, 6.0 g). DTPA anhydride (0.441 g) was added to the solution of the gluconate (2.17 g) in 20 mL of CH3CN and the mixture was refluxed for 2 h. After the completion of the reaction, the evaporation of the solvent gave DTPA derivative of bis(diethylenetriamine bisgluconate) (D1). D1 was dissolved in 3.5 mL Gd2O3(0.0123 g) solution in H2O/MeOH (2/1). The mixture was refluxed for 45 min. Work-up and removal of free Gd(III) ion gave Gd-D1 (0.15 g) in 95% yield). Uncomplexed Gd3+ ions were removed by treatment with Chelex. The absence of free Gd ions was checked by use of xylenol orange indicator.20
