Supramolecular aggregates of amphiphilic gadolinium complexes as blood pool MRI/MRA contrast agents: physicochemical characterization

Langmuir. 2006 Jul 18;22(15):6635-43. doi: 10.1021/la053500k.

Abstract

In this paper, we present the development of a new potential blood pool contrast agent for magnetic resonance imaging applications (MRA/MRI) based on gadolinium complexes containing amphiphilic supramolecular aggregates. A novel amphiphilic unimer, containing the DTPAGlu chelating agent covalently bound to two C18 alkylic chains, has been synthesized. DTPAGlu is a well-known chelating agent for a wide number of ions such as the paramagnetic metal ion Gd3+ used as contrast agent in MRA/MRI. The wide aggregation behavior of this surfactant, as free base or as gadolinium complex, has been studied and compared by means of dynamic light scattering, small-angle neutron scattering and cryogenic transmission electron microscopy techniques. Near neutral pH in both cases, the dominant aggregates are micelles. The high negative actual charge of the surfactant headgroup causes a strong headgroups repulsion, promoting the formation of large and high curvature aggregates. By decreasing pH and less markedly increasing the ionic strength, we observe a micelle-to-vesicle transition driven by a decreased electrostatic repulsion. A straightforward switch between different aggregation states can be particularly useful in the development of pH-responsive MRA/MRI contrast agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemical Phenomena
  • Chemistry, Physical
  • Contrast Media / chemistry*
  • Coronary Artery Disease / diagnosis
  • Gadolinium DTPA / chemical synthesis
  • Gadolinium DTPA / chemistry*
  • Gadolinium DTPA / pharmacokinetics
  • Hydrogen-Ion Concentration
  • Light
  • Macromolecular Substances / chemical synthesis
  • Macromolecular Substances / chemistry
  • Macromolecular Substances / pharmacokinetics
  • Magnetic Resonance Angiography / methods*
  • Microscopy, Electron, Transmission / methods
  • Molecular Structure
  • Neutron Diffraction
  • Particle Size
  • Scattering, Radiation
  • Scattering, Small Angle
  • Sensitivity and Specificity
  • Surface-Active Agents / chemical synthesis
  • Surface-Active Agents / chemistry*
  • Surface-Active Agents / pharmacokinetics

Substances

  • Contrast Media
  • Macromolecular Substances
  • Surface-Active Agents
  • Gadolinium DTPA