Amide conjugates of the DO3A-N-(alpha-amino)propionate ligand: leads for stable, high relaxivity contrast agents for MRI?

Abstract

A novel synthetic methodology for preparing amide conjugates of the DO3A-N-(alfa-amino)propionate chelator is described, using the synthesis of the DO3A-N-(alfa-benzoylamido)propionate chelator as an illustrative example. The model Gd(DO3A-N-(alfa-benzoylamido)propionate) chelate displays accelerated water exchange, stability in a wide pH range and inertness towards transmetallation by Zn2+. The Gd(DO3A-N-(alafa-benzoylamido)propionate) complex is mainly excreted via the kidneys, producing a significant increase of the kidney medulla/cortex enhancement ratio in MR images of Wistar rats, reflecting probably its increased hydrophobicity compared to Gd(DTPA). The results presented suggest that Gd(DO3A-N-(alfa-amido)propionate) chelates can be valuable leads for preparing potentially safe high relaxivity MRI contrast agents.