Compartmentalization of Gd liposomes: the quenching effect explained.

Cationic liposomes carrying high [Gd] can be used as efficient cell-labeling agents. In a compartmentalized state, Gd can cause signal loss (relaxivity quenching). The contributions of liposomal [Gd], size and compartmentalization state to relaxivity quenching were assessed. The dependency of signal intensity (SI) on intraliposomal [Gd] was assessed comparing three different [Gd] (0.3, 0.6 and 1.0M Gd) in both small (80nm) and large (120nm) cationic liposomes. In addition, five compartmentalization states were compared: free Gd, intact Gd liposomes, ruptured Gd liposomes, Gd liposomes in intact cells and Gd liposomes in ruptured cells (simulating cell death). Gd also causes R-2 effects, which is often overlooked. Therefore, both R-1 and R-2 relaxation rates of a dilution range were measured by T-1 and T-2 mapping on a 7T clinical scanner. Less is more. As the unidirectional water efflux rate (outbound across the liposome membrane, (le)) is proportional to the surface:volume ratio, smaller liposomes yielded a consistently higher R-1 than larger liposomes. For equal voxel [Gd] less concentrated liposomes (0.3M Gd) yielded higher R-1/R-2 ratio because of the higher extraliposomal water fraction (v(l)). Gd exhibits a dualistic behavior: from hypointensity to hyperintensity to hypointensity, with decreasing [Gd]. Regarding compartmentalization, fewer membrane barriers means a higher R-1/R-2 ratio. Gd liposomes exhibit a versatile contrast behavior, dependent on the compartmentalization state, liposomal size, intraliposomal [Gd] and liposome number. Both R1 and R2 effects contribute to this. The versatility allows one to tailor the optimal liposomal formulation to desired goals in cell labeling and tracking. Copyright (c) 2015 John Wiley & Sons, Ltd.