Dynamic changes in 1H-MR relaxometric properties of cell-internalized paramagnetic liposomes, as studied over a five-day period

Molecular imaging based on MRI requires the use of amplification strategies in order to achieve sufficient sensitivity for the detection of low-level molecular markers. Recently, we described a combination of two amplification methods: (i) the use of paramagnetic liposomes that can be prepared with a high payload of Gd3+-containing lipid; and (ii) targeting to a cell-surface receptor that can undergo multiple rounds of nanoparticle delivery in the cell, followed by recycling to the cell membrane. Liposome uptake was monitored over a period of 24 h and was found to lead to massive delivery in subcellular compartments. The present study aimed to monitor the longer-term fate of the cell-internalized contrast material by studying its relaxometric properties over 5 days, following an initial 24 h loading period. Circa 25% of the Gd3+-content delivered to the cells via integrin-targeted liposomes was lost in the first 24 h, which led to 65 and 77% reductions in R-1 and R-2, respectively, as compared with the original R-1 and R-2 enhancements. This implies that the remaining cell-associated gadolinium had relatively low effective r(1) and r(2) relaxivities. It is proposed that this is due to gradual release of Gd3+ from the chelate in the cell, followed by sequestration in an MR silent state. Most of the gadolinium internalized by cells following incubation with non-targeted liposomes was released in the 5-day follow-up period. Copyright (C) 2010 John Wiley & Sons, Ltd.