The relative hydrolytic stability of contrast agents for magnetic resonance imaging (MRI). consisting of paramagnetic metal chelates bound to polysaccharides through an ester bond, has been investigated. Four preparations of biodegradable, cross-linked starch particles were studied as model compounds: diethylenetriaminepentaacetic acid (DTPA)-starch particles (1), two batches of gadolinium-DTPA (GdDTPA)-starch particles (2a,2b) with different Gd content, and N-(2-phenylethyl)succinamoyl starch ester particles (4). In a study of hydrolytic rates in water suspension, the derivatives with GdDTPA bound directly to the particle via the carboxylic acid groups in DTPA (2a,2b) showed 74 and 86% remaining matrix-bound GdDTPA, respectively, alter 21 days. The unchelated derivative (1) showed 96% remaining matrix-bound DTPA, while for the succinamoyl-linked derivative (4), no significant hydrolysis took place during the same time span. To investigate the corresponding stability of ester bonds in water-soluble, blood-pool agents for MRI, the degradation rate of the macromolecular derivatives dextran-DTPAGd ( 5) and dextran--/3-alanine-DTPAGd (6c) were compared in artificial blood plasma. The remaining fraction of undegraded ester bond in 6c was approximately 95% after 100 min, while 5 was approximately fully degraded over the same time span. These results indicate that the conjugate with the /3-alanine spacer may have a more suitable degradation rate for blood-pool MRI contrast purposes than the derivatives with GdDTPA directly ester bound. It was also shown by relaxation measurements that gadolinium-ethylenediaminetetraacetic acid (GdEDTA) was demetalated in a test solution of phosphate (3 raM) at 37 °C. No demetalation was observed for GdDTPA derivatives of water-soluble polysaccharides, represented by the dextran-GdDTPA conjugate 5