MRI Contrast Agents Based On Cyclen With Tethered Quaternary Ammonium Groups

Magnetic resonance imaging (MRI) has been utilized in various field benefited from its superior spatial resolution and contrast since1973, Contrast-enhancing agents (CAs), functioned as an important part of MRI, usually being gadolinium (Ⅲ) complexes, have gained enormous. Loading of small molecular CAs on bigger objects is a generally admitted method to accelerate the relaxation rate of water molecules, however with sacrificing the solubility of these CAs in water.Functionalizing small molecular CAs without affecting their solubility to enhance relaxivity still constitue a great challenge.Currently used clinical MRI CAs are small molecules like [Gd-DOTA(H2O)](Dotarem). Hence to fuctionalize current clinical Gd(III) complexes become the most pratical and potential methodology for improvement. Gd(III)-DOTA serve as a practical precursor for functionalization due to its high thermodynamic and kinetic stability endowed by the coordination pocket. In this study, a new series of MRI CAs with tethered quaternary ammonium groups were synthesized.The quaternary ammonium group was introduced in the skeleton of1,4,7,10-tetraazacyclododecane (cyclen), and the four secondary amino groups in cyclen was functionalized with carboxymethyl groups, forming polychelating ligand with quaternary ammonium side chain. The Gd(III) complexes of these ligands showed higher water solubility and higher relaxivity than Gd(III)-DOTA. With both quaternary ammonium group and long alkyl chain installed in the same molecule, further functionalization or modification to achieve high performance MRI contrast agents is promising.