期刊
JOURNAL OF MATERIALS CHEMISTRY
卷 21, 期 34, 页码 12917-12926出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c1jm00005e
关键词
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资金
- PolitiqueScientifiqueFederale [IAP VI/27]
- National Funds for Scientific Research (F.R.S.-FNRS)
- University of Liege
- FNRS
- IISN of Belgium
Conventional low molecular weight gadolinium based Magnetic Resonance Imaging (MRI) contrast agents such as Magnevist (R) are very useful for imaging tissues. However, at the high magnetic fields used in modern MRI equipments, their relaxivity (contrasting efficiency) is rather poor. The grafting of the gadolinium complex onto macromolecules is a way to enhance their relaxivity provided that the rotational motion of the complex is decreased significantly. Here we report the design of novel Gd3+ based MRI contrast agents with improved relaxivity and potential long blood circulation life-time. We investigate the grafting of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, 1,4,7-tris(1,1-dimethylethyl) ester (DO3AtBu-NH2; a precursor of Gd3+ ligand) onto well-defined functional copolymers bearing activated esters (succinimidyl esters) and poly(ethylene oxide) (PEO) chains required for stealthiness. The tert-butyl groups of grafted DO3AtBu-NH2 are then deprotected by trifluoroacetic acid followed by complexation of Gd3+. Addition of free DOTA at the end of the reaction is necessary to leave the pure and stable water soluble macrocontrast agent. Importantly it shows a relaxivity at high frequencies that is 300% higher than that of the ungrafted gadolinium complex. These novel functional copolymers are therefore promising candidates as macromolecular contrast agents for MRI applications.
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