Supramolecular aggregates of amphiphilic gadolinium complexes as blood pool MRI/MRA contrast agents: physicochemical characterization.
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.
Vaccaro
Mauro
M
Department of Chemistry, University of Naples Federico II, Via Cynthia, 80126 Naples, Italy.
Accardo
Antonella
A
Tesauro
Diego
D
Mangiapia
Gaetano
G
Löf
David
D
Schillén
Karin
K
Söderman
Olle
O
Morelli
Giancarlo
G
Paduano
Luigi
L
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003287:Contrast Media / Q000737:chemistry*; D003324:Coronary Artery Disease / Q000175:diagnosis; D019786:Gadolinium DTPA / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D008027:Light; D046911:Macromolecular Substances / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D018810:Magnetic Resonance Angiography / Q000379:methods*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D015394:Molecular Structure; D033363:Neutron Diffraction; D010316:Particle Size; D012542:Scattering, Radiation; D053838:Scattering, Small Angle; D012680:Sensitivity and Specificity; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
D003287:Contrast Media; D046911:Macromolecular Substances; D013501:Surface-Active Agents; D019786:Gadolinium DTPA