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Journal of Lipid Research, Vol. 50, 2157-2163, November 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis

Andrei Maiseyeu^*, Georgeta Mihai^*, Thomas Kampfrath^*, Orlando P. Simonetti^*, Chandan K. Sen, Sashwati Roy^*, Sanjay Rajagopalan^* and Sampath Parthasarathy^1,

^* Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH
Department of Surgery, Ohio State University, Columbus, OH

¹ To whom correspondence should be addressed. e-mail: spartha{at}osumc.edu

Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent an attractive approach for molecular imaging of atherosclerosis. We investigated the utility of paramagnetic gadolinium liposomes enriched with PS (Gd-PS) in imaging atherosclerotic plaque. Gd-PS-containing Gd-conjugated lipids, fluorescent rhodamine, and PS were prepared and characterized. Cellular uptake in RAW macrophages (fluorescent uptake of rhodamine) was studied on a fluorescence plate reader, while Gd-PS-induced alteration in T1 relaxivity was evaluated using a 1.5 T MRI scanner. RAW cells demonstrate PS-dependent uptake of across a range of concentrations (2, 6, 12, and 20%) in comparison to control liposomes with no PS (0%). In vivo performance of Gd-PS was evaluated in the ApoE^–/– mouse model by collection of serial T1 weighted gradient echo MR images using an 11.7 T MRI system and revealed rapid and significant enhancement of the aortic wall that was seen for at least 4 h after injection. Gd-PS-enriched liposomes enhance atherosclerotic plaque and colocalize with macrophages in experimental atherosclerosis.

Supplementary key words macrophages • apoptosis mimicking • cellular uptake • colocalization with macrophages • ApoE^–/– mouse model

Abbreviations: DOPE-Rho, phosphatidylethanolamine-Lissamine-Rhodamine B; Gd, gadolinium; Gd-DTPA-SA, Gd-diethylenetriaminepentaacetic acid distearylamide; LDH, lactate dehydrogenase; MSR, macrophage scavenger receptor; NENH, normalized enhancement; PC, phosphatidylcholine; PEG, polyethyleneglycol; PG, phosphatidylglycerol; PS, phosphatidylserine; SNR, signal-to-noise ratio

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