Advances in Metal-Based Probes for MR Molecular Imaging Applications

E.      Terreno; W.      Dastru; D.      Delli Castelli; E.      Gianolio; S.      Geninatti Crich; D.      Longo; S.      Aime

Abstract

The role of MRI in the armory of diagnostic modalities for the medicine of the forthcoming years largely depends on how chemistry will provide advanced tools to meet the medical needs. This review aims at outlining the most innovative approaches that have been undertaken in the recent history of MRI contrast agents for tackling the challenges of sensitivity and specificity required by the new generation of contrast agents that should allow the visualization of pathological processes occurring on cellular and molecular scale (the so-called Molecular Imaging). Most of the classes of MRI agents clinically approved or currently under investigation in a preclinical phase exploit peculiar magnetic properties of metals. The conventional agents acting as T1 or T2/T2* relaxation enhancers are primarily based on the paramagnetic or the superparamagnetic properties of Gd(III)-, Mn(II)- and iron oxides systems. Recently, there has been a renewed interest towards paramagnetic lanthanide complexes with an anisotropic electronic configuration thanks to their ability to induce strong effect on the resonance frequency of the spins dipolarly coupled with them. Such systems, formerly mainly used as shift reagents, have now attracted much attention in the emerging field of Chemical Exchange Saturation Transfer (CEST) MRI agents.

Keywords: MRI, molecular imaging, contrast agents, lanthanide, iron oxides, CEST, liposomes, MR Molecular Imaging, peculiar magnetic properties, Chemical Exchange Saturation Transfer (CEST) MRI agents, Resonance Imaging (MRI) methodology, Gd-complex, symptomatic phase, superparamagnetic iron oxide (SPIO), Gd-BASED AGENTS, Solomon-Bloembergen-Morgan theory, AAZTA, Gd-DTPA, Gd-DOTA, metal-based nanoparticles, inner apoferritin cavity, nanocarriers, amphiphilic metal complex, biotinlylated Gd-loaded apoferritin, streptavidin, biotinylated targeting vector recognizing, C3d-Bio/streptavidin/Gd-loaded apoferritin, galactopyranosyl moiety, poly--cyclodextrin, Nanotechnology, Fe-HBED, microemulsions, sol-gel syntheses, sonochemical reactions, hydrothermal, reactions, hydrolysis, thermolysis of precursors, named CLIO, antibodies, oligonucleotides, specific off-resonance, nanoparticles, GADOLINIUM