Gadolinium−based Contrast Agents
The perturbation on the relaxation of solvent water protons induced by the presence of paramagnetic metal-containing systems has been exploited for the design of contrast agents
in Magnetic Resonance Imaging applications. Complexes of Gd3+ ion have been early identified as the candidates of choice and several, highly stable, Gd-containing contrast agents
have entered in the clinical practice already two-three decades ago. Basically Gd-complexes are chemicals that affect the relaxation rates (R1 and R2) of the water protons in
the regions where they distribute. Actually, Gd3+ ion (seven unpaired electrons, long electronic relaxation time) was immediately recognized as the paramagnetic ion of choice.
Moreover, the coordination chemistry of this metal ion was already sufficiently known and several ligands (in particular polyamino-polycarboxylates) were already proved to be able to wrap around the Gd3+ ion to form highly stable complexes. The requirement of a high thermodynamic (and kinetic) stability is a key requisite for these complexes to be considered as potential CAs for in vivo applications.
The chemistry of Gd-complexes is one of the first research line which has been tackled at CIM. It starts from the synthesis of differently functionalized Gd-based probes and continues to their relaxometric characterization for the in depth elucidation of the relationships between structure and dynamics of paramagnetic metal complexes and the determinants of their proton relaxation enhancement. Moreover, all the new Gd-complexes which are here synthetized and characterized are tested for their specific function in vitro (at the cellular level) and/or in vivo (in specific animal models).
On this basis, at CIM a number of Gd-containing complexes are synthetized and tested:
- Small-molecular weight Gd-complexes
Unspecific hydrophilic chemicals to visualize tumor perfusion or abnormalities in organ function or as responsive agents to tissue microenvironment parameters.
- Blood-pool agents
Gd-complexes functionalized with hydrophobic moieties which enable the binding to human serum albumin in order to increase relaxivity and the retention time in blood vessels. These complexes find application also in quantitative assessments of tumor angiogenesis by exploiting DCE-MRI (Dynamic Contrast Enhanced-MRI) approaches.
- Macromolecular agents
Gd-complexes are incorporated in high molecular weight systems either as part of supramolecular assemblies such as liposomes or micelles and as multimers of Gd-complexes (dimers, tetramers, dendrimers).