Journal
MAGNETIC RESONANCE IN MEDICINE
Volume 61, Issue 5, Pages 1022-1032Publisher
JOHN WILEY & SONS INC
DOI: 10.1002/mrm.21910
Keywords
MRI; relaxation; relaxivity; quenching; paramagnetic contrast agent; liposomes; HUVEC; gadolinium; molecular imaging
Funding
- BSIK [BSIK03033, EC-FP6, LSHB-CT-2005-512146]
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In recent years, numerous Gd(3+)-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 size- able amount of contrast agent into the target cell. An example of such a membrane receptor is the alpha(nu)beta(3) integrin. The goal of this study was to investigate the consequences of this amplification approach for the T(1)- and T(2)-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 alpha(nu)beta(3) integrin receptor. Non-targeted liposomes served as a control. This study showed that alpha(nu)beta(3) 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 61:1022-1032, 2009. (C) 2009 Wiley-Liss, Inc.
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