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

Contrast Media Mol Imaging. 2013 Jan-Feb;8(1):40-9. doi: 10.1002/cmmi.1492.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chelating Agents* / chemical synthesis
  • Chelating Agents* / chemistry
  • Chelating Agents* / pharmacology
  • Contrast Media* / chemical synthesis
  • Contrast Media* / chemistry
  • Contrast Media* / pharmacology
  • Heterocyclic Compounds, 1-Ring* / chemical synthesis
  • Heterocyclic Compounds, 1-Ring* / chemistry
  • Heterocyclic Compounds, 1-Ring* / pharmacology
  • Hydrogen-Ion Concentration
  • Ligands
  • Magnetic Resonance Imaging / methods*
  • Male
  • Rats
  • Rats, Wistar
  • Zinc / chemistry

Substances

  • 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid
  • Chelating Agents
  • Contrast Media
  • Heterocyclic Compounds, 1-Ring
  • Ligands
  • Zinc