Facile synthesis and in vivo evaluation of biodegradable dendritic MRI contrast agents

Dendritic gadolinium chelates as magnetic resonance imaging (MRI) contrast agents (CAs) have shown great potential in blood pool and tumor imaging due to their enhanced relaxivities (R(1)s), prolonged blood circulation time, and homogeneous pharmaceutical properties. However, the non-biodegradability of the currently used dendrimers causes long-term retention of toxic gadolinium ions, limiting their clinical applications. Herein, we report a facile synthesis of biodegradable polyester dendrimer-based CAs. The prepared dendritic CAs have nano-sized structures with the hydrodynamic diameters ranging from 2.8 to 8.6 nm, and show high R(1)s up to 11.7 mM(-1) s(-1), approximately 2.7 times that of a clinically used small molecule CA (Magnevist). They are slowly hydrolyzed at an acidic pH, but rapidly hydrolyzed at pH 7.4, especially in the presence of esterase. The in vivo evaluation indicates they not only provide much better MRI contrast enhancement than Magnevist, but also show minimal tissue retention of Gd, which is much lower than those of non-biodegradable CAs.