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 1.0 M Gd) in both small (80 nm) and large (120 nm) 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 R2 effects, which is often overlooked. Therefore, both R1 and R2 relaxation rates of a dilution range were measured by T1 and T2 mapping on a 7 T clinical scanner. Less is more. As the unidirectional water efflux rate (outbound across the liposome membrane, κle) is proportional to the surface:volume ratio, smaller liposomes yielded a consistently higher R1 than larger liposomes. For equal voxel [Gd] less concentrated liposomes (0.3 M Gd) yielded higher R1/R2 ratio because of the higher extraliposomal water fraction (vl ). Gd exhibits a dualistic behavior: from hypointensity to hyperintensity to hypointensity, with decreasing [Gd]. Regarding compartmentalization, fewer membrane barriers means a higher R1 /R2 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.