Paramagnetic liposomes as MRI contrast agents: Influence of liposomal physicochemical properties on the in vitro relaxivity

The in vitro contrast efficacy of liposome encapsulated gadolinium-[10-(2-h ydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid] (GdHPDO3 A) has been assessed by relaxometry. The internal concentrations were 150 a nd 250 mM Gd. Two types of liposome compositions were investigated: a phosp holipid blend consisting of both hydrogenated phosphatidylcholine (HPC) and phosphatidylserine (HPS) with a gel-to-liquid crystalline phase transition temperature (T-m) of 50 degrees C, and a mixture of dipalmitoylphosphatidy lcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) with a T-m of 41 degrees C. The investigated liposome size range was 70-400 mm. The T-1 and T-2 relaxivities (r(1) and r(2)) of liposome encapsulated GdHPDO3A were si gnificantly reduced at 37 degrees C and 0.47 T, compared to those of non-li posomal metal chelate, due to an exchange limitation of the dipolar relaxat ion process. The highest relaxivity values were obtained for the DPPC/DPPG liposomes, and were attributed to a higher liposome water permeability and to a more efficient water exchange across the membrane. A reduction in lipo some size increased the r(1), confirming the exchange limited dipolar relax ation. The increased r(1) with increasing temperature demonstrated the prer equisite of rapid water exchange between the interior and exterior of the l iposome for efficient dipolar relaxation enhancement. Susceptibility effect s were present in the liposome systems as the r(2)/r(1) ratio increased wit h increasing liposome size and internal Gd concentration. In summary, the c urrent work has shown the influence of key physicochemical properties, such as liposome size, membrane composition and permeability, on the in vitro r elaxivity of liposome encapsulated GdHPDO3A. (C) 1998 Elsevier Science Inc.