Novel radical-responsive MRI contrast agent based on paramagnetic liposomes

A novel, radical responsive MRI contrast agent based on a gadolinium chelate conjugated to a liposome through a disulfide linker was synthesized, with the aim of pursuing the in vivo mapping of radicals. The liposome was prepared by incorporating a thiol-activated phospholipid, which was subsequently reacted with a gadolinium chelate containing a free thiol group. The long reorientational motion of the supramolecular adduct endows the paramagnetic agent with a relaxivity significantly higher than that of the free complex. The disulfide bond represents a radical-sensitive moiety and a large decrease in contrast efficacy (T-1 relaxivity) is shown upon its cleavage. A preliminary assessment of the system was made by means of in vitro gamma-irradiation and thiol-disulfide bond exchange with dithiothreitol. Both methods showed a clear dose-dependent decrease in T-1-relaxivity. Copyright (C) 2003 John Wiley Sons, Ltd.