Cellular compartmentalization of internalized paramagnetic liposomes strongly influences both T1 and T2 relaxivity

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Abstract
In recent years, numerous Gd3+-based contrast agents have been developed to enable target-specific MR imaging of in vivo processes at the molecular level. The combination of powerful contrast agents and amplification strategies, aimed at increasing the contrast agent dose at the target site, is an often-used strategy to improve the sensitivity of biomarker detection. One such amplification mechanism is to target a disease-specific cell membrane receptor that can undergo multiple rounds of internalization following ligand binding and thus shuttle a sizeable amount of contrast agent into the target cell. An example of such a membrane receptor is the ανβ3 integrin. The goal of this study was to investigate the consequences of this amplification approach for the T1- and T2-shortening efficacy of a paramagnetic contrast agent. Cultured endothelial cells were incubated with paramagnetic liposomes that were conjugated with a cyclic RGD-peptide to enable internalization by means of the ανβ3 integrin receptor. Non-targeted liposomes served as a control. This study showed that ανβ3 targeting dramatically increased the uptake of paramagnetic liposomes. This targeting strategy, however, strongly influenced both the longitudinal and transverse relaxivity of the internalized paramagnetic liposomes. Magn Reson Med, 2009.