Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG-micelles.
Pegylated, fluorescent, and paramagnetic micelles were developed. The micelles were conjugated with macrophage scavenger receptor (MSR)-specific antibodies. The abdominal aortas of atherosclerotic apoE-KO mice were imaged with T(1)-weighted high-resolution MRI before and 24 h after intravenous administration of the contrast agent (CA). Pronounced signal enhancement (SE) (up to 200%) was observed for apolipoprotein E knockout (apoE-KO) mice that were injected with MSR-targeted micelles, while the aortic vessel wall of mice injected with nontargeted micelles showed little SE. To allow fluorescence microscopy and optical imaging of the excised aorta, the micelles were made fluorescent by incorporating either a quantum dot (QD) in the micelle corona or rhodamine lipids in the micelle. Ultraviolet (UV) illumination of the aorta allowed the identification of regions with high macrophage content, while MSR-targeted rhodamine micelles could be detected with fluorescence microscopy and were found to be associated with macrophages. In conclusion, this study demonstrates that macrophages in apoE-KO mice can be effectively and specifically detected by molecular MRI and optical methods upon administration of a pegylated micellar CA.
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Willem J M
WJ
Mulder
Gustav J
GJ
Strijkers
Karen C
KC
Briley-Saboe
Juan C
JC
Frias
Juan Gilberto S
JG
Aguinaldo
Esad
E
Vucic
Vardan
V
Amirbekian
Cheuk
C
Tang
Patrick T K
PT
Chin
Klaas
K
Nicolay
Zahi A
ZA
Fayad
D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D003287:Contrast Media; D004337:Drug Carriers / Q000737:chemistry; D019786:Gadolinium DTPA / Q000737:chemistry; D007089:Image Enhancement / Q000379:methods*; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*
D003287:Contrast Media; D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D019786:Gadolinium DTPA