Compartmentalization of Gd liposomes: the quenching effect explained

Area of Science:

• Biomedical imaging
• Nanotechnology
• Materials science

Background:

• Cationic liposomes loaded with Gadolinium (Gd) are effective cell-labeling agents.
• Gd's relaxivity is influenced by compartmentalization, leading to signal loss.
• Both R1 and R2 relaxation effects of Gd are crucial for contrast behavior.

Purpose of the Study:

• To investigate the impact of liposomal Gd concentration, size, and compartmentalization on relaxivity quenching.
• To assess the signal intensity dependency on intraliposomal Gd concentration.
• To understand the interplay of R1 and R2 effects in Gd-based contrast agents.

Main Methods:

• Comparison of three intraliposomal Gd concentrations (0.3, 0.6, 1.0 M) in small (80 nm) and large (120 nm) liposomes.
• Evaluation of five compartmentalization states: free Gd, intact liposomes, ruptured liposomes, liposomes in intact cells, and liposomes in ruptured cells.
• Measurement of R1 and R2 relaxation rates using T1 and T2 mapping on a 7T clinical scanner.

Main Results:

• Smaller liposomes (80 nm) consistently showed higher R1 values due to increased surface:volume ratio and water efflux.
• Lower liposome concentrations (0.3 M Gd) resulted in a higher R1/R2 ratio due to a larger extraliposomal water fraction.
• Gd exhibited dualistic contrast behavior (hypointense to hyperintense to hypointense) dependent on concentration.
• Reduced membrane barriers (e.g., ruptured liposomes) increased the R1/R2 ratio.

Conclusions:

• Gd liposome contrast behavior is highly versatile, tunable by liposomal size, intraliposomal Gd concentration, and compartmentalization.
• Both R1 and R2 relaxation effects are significant contributors to the observed contrast.
• This versatility enables optimization of liposomal formulations for specific cell labeling and tracking applications.