title: Amide conjugates of the DO3A-N-(α-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-(α-amino)propionate chelator is described, using the synthesis of the DO3A-N-(α-benzoylamido)propionate chelator as an illustrative example. The model Gd[DO3A-N-(α-benzoylamido)propionate] chelate displays accelerated water exchange, stability in a wide pH range and inertness towards transmetallation by Zn(2+). 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(DTPA). The results presented suggest that Gd[DO3A-N-(α-amido)propionate] chelates can be valuable leads for preparing potentially safe high relaxivity MRI contrast agents.
authors.affiliation: Centro de Química, Campus de Gualtar, Universidade do Minho, Braga, Portugal.
authors.forename: Miguel F
authors.initials: MF
authors.lastname: Ferreira
authors.forename: André F
authors.initials: AF
authors.lastname: Martins
authors.forename: Catarina I O
authors.initials: CI
authors.lastname: Martins
authors.forename: Paula M
authors.initials: PM
authors.lastname: Ferreira
authors.forename: Eva
authors.initials: E
authors.lastname: Tóth
authors.forename: Tiago B
authors.initials: TB
authors.lastname: Rodrigues
authors.forename: Daniel
authors.initials: D
authors.lastname: Calle
authors.forename: Sebastian
authors.initials: S
authors.lastname: Cerdan
authors.forename: Pilar
authors.initials: P
authors.lastname: López-Larrubia
authors.forename: José A
authors.initials: JA
authors.lastname: Martins
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000737:chemistry
chemical_list: C520644:1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid; D002614:Chelating Agents; D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D015032:Zinc