title: Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis.
abstract: 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.
authors.affiliation: Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Maiseyeu
authors.forename: Georgeta
authors.initials: G
authors.lastname: Mihai
authors.forename: Thomas
authors.initials: T
authors.lastname: Kampfrath
authors.forename: Orlando P
authors.initials: OP
authors.lastname: Simonetti
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Sampath
authors.initials: S
authors.lastname: Parthasarathy
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003287:Contrast Media / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D057054:Molecular Imaging / Q000379:methods; D010718:Phosphatidylserines / Q000737:chemistry*; D012680:Sensitivity and Specificity
chemical_list: D001057:Apolipoproteins E; D003287:Contrast Media; D008081:Liposomes; D010718:Phosphatidylserines; D005682:Gadolinium