MRI contrast agents for very high magnetic fields

• Forschungsstelle: COST
• Projektnummer: C06.0072
• Projekttitel Englisch: MRI contrast agents for very high magnetic fields

Schlüsselwörter (Englisch)

magnetic resonance imaging (MRO); contrast agents; high relaxivity; high magnetic field; NMR; nuclear magnetic relaxation dispersion

Forschungsprogramme (Englisch)

COST-Action D38 - Meta-based Systems for Molecular Imaging Applications

Kurzbeschreibung (Englisch)

This research proposal is directed to the development of new contrast agents for application at very high magnetic field. Two parallel lines of compounds will be synthesized and analyzed for their physico-chemical properties within the project. The first line comprises medium size polyaminocarboxylate complexes of gadolinium(III) bearing a maximum of paramagnetic ions. The goal is to achieve a high local molecular density of relaxation even at magnetic fields above 3T. The second line of compounds is based on gadolinium carbon nanotubes where a very high relaxivity at high magnetic field has been found in preliminary experiments. A full understanding of the physico-chemical properties responsible for the unusual magnetic field dependence of this compound is essential for further development and perhaps a compound with even higher relaxivity.

Partner und Internationale Organisationen (Englisch)

BE, CH, CY, CZ, DE, ES, FI, FR, GR, HU, IT, NL, PL, PT, UK

Abstract (Englisch)

ln the past two decades clinical MRI developed very fast. The search for higher spatial resolution and better sensitivity led to the development of 3 T systems which became rapidly available in clinics. The increasing availability of high-field systems in clinics and the advent of ultrahigh-field systems in research raise the question on MRI contrast agents at high magnetic fields. The research for very high magnetic field MRI contrast agents has been directed in two directions: - Optimization of longitudinal relaxation enhancement per Gd3+-ion, the relaxivity, at magnetic fields above 3 T - Creating molecules and particles carrying many paramagnetic centers on a relatively small volume. Rational design of new contrast agents with higher eelaxivity is possible as a result of a better understanding of the underlying relaxation mechanisms. Quantum chemical calculations together with molecular dynamics simulations allow obtaining fundamental parameters such as quadrupole coupling constants and hyperfine interaction tensors directly at a molecular level. A large comparative study has shown that the new theoretical descriptions of relaxation enhancement by paramagnetic ions developed by Fries et alleads to results similar to those of the Swedish model. Various new metal chelators have been tested for its use in contrast agents. Main emphasis has been on accelerated water exchange, on the possibility to bind two water molecules and the prospect to form supramolecular assemblies. A series of dendrimers loaded at their surface with macrocyclic Gd-chelates have been characterized in vitro and in vivo. From studies on benzene-and ruthenium-based structures it has been concluded that at fields above 3T best relaxivities can be achieved with mid-size molecules with molecular tumbling times between 0.5 and 1 ns. Aggregates with three and six Gd3+-ions have been successfully tested and show better contrast enhancement at 4.7 T than commercial Gd-DOTA. Gold nanoparticles assembling more than 50 paramagnetic centers at the surface have been synthesized and tested in vitro. The size of the particles is still small (mean diameters of -5 nm) so that these compounds can leave the blood vessels. The density of Gd-chelates at the surface is very high and therefore the particles behave as rigid units with little internal mobility.

Datenbankreferenzen (Englisch)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C06.0072