Dynamic changes in 1 H‐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 Gd 3+ ‐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 Gd 3+ ‐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 Gd 3+ 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 © 2010 John Wiley & Sons, Ltd.