Amide conjugates of the DO3A-N-(alfa-amino)propionate ligand : leads for stable...

• Author(s): Ferreira, Miguel Filipe Moreira Marques ; Martins, André F. ; Martins, Catarina I. O. ; Ferreira, Paula M. T. ; Tóth, Éva ; Rodrigues, Tiago B. ; Calle, Daniel ; Cerdan, Sebastian ; López-Larrubia, Pilar ; Martins, José A. ; Geraldes, Carlos F. G. C.
• Date: 2013
• Persistent ID: http://hdl.handle.net/1822/27355
• Origin: RepositóriUM - Universidade do Minho
• Subject(s): DO3A-N-(alfa-amido)propionate chelators; Gd[DO3A-N-(alfa-benzoylamido)propionate] chelate; Fast water exchange; pH stability; Safety; in vivo MRI
• Document Type: Article
• Language: English

Description

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.