title: Detection of vulnerable atherosclerosis plaques with a dual-modal single-photon-emission computed tomography/magnetic resonance imaging probe targeting apoptotic macrophages.
abstract: Atherosclerosis (AS), especially the vulnerable AS plaque rupture-induced acute obstructive vascular disease, is a leading cause of death. Accordingly, there is a need for an effective method to draw accurate predictions about AS progression and plaque vulnerability. Herein we report on an approach to constructing a hybrid nanoparticle system using a single-photon-emission computed tomography (SPECT)/magnetic resonance imaging (MRI) multimodal probe, aiming for a comprehensive evaluation of AS progression by achieving high sensitivity along with high resolution. Ultrasmall superparamagnetic iron oxide (USPIO) was covered by aminated poly(ethylene glycol) (PEG) and carboxylated PEG simultaneously and then functionalized with diethylenetriaminepentacetate acid for (99m)Tc coordination and subsequently Annexin V for targeting apoptotic macrophages abundant in vulnerable plaques. The in vivo accumulations of imaging probe reflected by SPECT and MRI were consistent and accurate in highlighting lesions. Intense radioactive signals detected by SPECT facilitated focus recognization and quantification, while USPIO-based T2-weighted MRI improved the focal localization and volumetry of AS plaques. For subsequent ex vivo planar images, targeting effects were further confirmed by immunohistochemistry, including CD-68 and TUNEL staining; meanwhile, the degree of concentration was proven to be statistically correlated with the Oil Red O staining results. In conclusion, these results indicated that the Annexin V-modified hybrid nanoparticle system specifically targeted the vulnerable AS plaques containing apoptotic macrophages and could be of great value in the invasively accurate detection of vulnerable plaques.
authors.affiliation: Department of Nuclear Medicine and ∥Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University , Shanghai 200032, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cheng
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Chunfu
authors.initials: C
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Tan
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Lifang
authors.initials: L
authors.lastname: Pang
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Shi
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology*; D003911:Dextrans / Q000737:chemistry; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000000981:diagnostic imaging / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic; D011859:Radiography; D014055:Tomography, Emission-Computed
chemical_list: D017304:Annexin A5; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10
keywords: Annexin V; SPECT/MRI; apoptotic macrophage; atherosclerosis; hybrid nanoparticle system; vulnerable plaque