Amide conjugates of the DO3A-N-(α-amino)propionate ligand: leads for stable, high relaxivity contrast agents for MRI? (pages 40–49)
Miguel F. Ferreira, André F. Martins, Catarina I. O. Martins, Paula M. Ferreira, Éva Tóth, Tiago B. Rodrigues, Daniel Calle, Sebastian Cerdan, Pilar López-Larrubia, José A. Martins and Carlos F. G. C. Geraldes
Article first published online: 29 OCT 2012 | DOI: 10.1002/cmmi.1492
A novel synthetic methodology for preparing amide conjugates of the DO3A-N-(α-amino)propionate chelator is described. The Gd[DO3A-N-(α-benzoylamido)propionate] chelate retains the fast water exchange and stability properties of its parent Gd[DO3A-N-(α-amino)propionate] chelate. The Gd[DO3A-N-(α-benzoylamido)propionate] complex is mainly excreted via the kidneys, producing a significant increase in the kidney medulla/cortex enhancement ratio in MR images of Wistar rats, reflecting probably its higher lipophilicity compared with Gd(DOTA). Macromolecular conjugates might allow combination of high relaxivities with stability for potentially safe in vivo applications.