Study on Gadolinium Complexes Based on Polysaccharide Derivatives as a Contrast Agent for MRI

The authors report new gadolinium compounds, polysaccharide-gadolinium chelate, that have the enhancement property in magnetic resonance imaging (MRI) as well as a longer half-life time in blood. Dialdehyde starch (DAS; mol. wt.7 x103) and dialdehyde amylose (DAA; mol. wt.3 x108) were synthesized to increase the half-life time in blood. The binding of gadolinium to DAS or DAA was facilitated by the newly synthesized bifunctional chelating agents N-[2-bis(carboxymethyl)arainoethyl]-N-[2-bis (carboxymethyl) amino-2-(p-benzyl) ethyl]glycine (ABDTPA) and 10-[N-(2-amin. oethyl)carbamoyl]methyl-a, a', a"-trimethy1-1, 4, 7, 10tetraazacyclododecane-1, 4, 7-triacetic acid (DO 3 MA). The enhancement properties of resifting gadoli nium compoumds were evaluated for biodistribution, relaxivity and enhancement effect. Biodistribution was dxamined by use of "In labelled complex. Relaxivity was measured at 0.5 T and 1.5 T. Enhancement effect was examined in vivo by using rats that have brain occlusions. Gadolinium(Gd) complexes with DAS or DAA were found to be staying in the blood vessel for a longer period of time than other existing enhancers. The half-life time of DAS-ABDTPA-Gd is 2 h, while as DAA-ABDTPA-Gd is 55 min. eighty to ninety percent of gadolinium complexes bound to DAS or DAA were excreted in urine 24 11 after administration. Relaxivities of the above gadolinium complexes were 1.2-2times as high as those of ABDTPA-Gd or DO 3 MA-Gd. These results demonstrate that gadolinium complexes based on polysaccharide derivatives are promising compounds for future use as MRI enhancers.