title: MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor.
abstract: The ability to specifically image macrophages may enable improved detection and characterization of atherosclerosis. In this study we evaluated the in vitro uptake of gadolinium (Gd)-containing immunomicelles (micelles linked to macrophage-specific antibody), micelles, and standard contrast agents by murine macrophages, and sought to determine whether immunomicelles and micelles improve ex vivo imaging of apolipoprotein E knockout (ApoE KO) murine atherosclerosis. Murine RAW 264.7 macrophages were incubated with Gd-DTPA, micelles, and immunomicelles. Cell pellets were prepared and imaged using a 1.5 T MR system with an inversion recovery spin-echo sequence to determine the in vitro T1 values. Ex vivo analysis of mouse aortas was performed using a 9.4T MR system with a high-spatial-resolution sequence (78x39x78 microm3). The T1 value was significantly decreased in cells treated with micelles compared to Gd-DTPA (P<0.0001), and in cells incubated at 4 degrees C with immunomicelles compared to micelles (P<0.05). Ex vivo MRI signal intensity (SI) was significantly increased by 81% and 20% in aortas incubated with immunomicelles and micelles, respectively. Confocal microscopy demonstrated in vitro and ex vivo uptake of fluorescent immunomicelles by macrophages. Immunomicelles and micelles improve in vitro and ex vivo MR detection of macrophages, and may prove useful in the detection of macrophage-rich plaques.
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lipinski
authors.forename: Vardan
authors.initials: V
authors.lastname: Amirbekian
authors.forename: Juan C
authors.initials: JC
authors.lastname: Frias
authors.forename: Juan Gilberto S
authors.initials: JG
authors.lastname: Aguinaldo
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Mani
authors.forename: Karen C
authors.initials: KC
authors.lastname: Briley-Saebo
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: John T
authors.initials: JT
authors.lastname: Fallon
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism*; D003287:Contrast Media / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D006571:Heterocyclic Compounds / Q000276:immunology / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008657:Metabolic Clearance Rate; D051379:Mice; D018345:Mice, Knockout; D008823:Micelles; D009942:Organometallic Compounds / Q000276:immunology / Q000493:pharmacokinetics*; D051116:Receptors, Scavenger / Q000276:immunology / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D008823:Micelles; D009942:Organometallic Compounds; D051116:Receptors, Scavenger; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate