title: 99mTc-labelled anti-CD11b SPECT/CT imaging allows detection of plaque destabilization tightly linked to inflammation.
abstract: It remains challenging to predict the risk of rupture for a specific atherosclerotic plaque timely, a thrombotic trigger tightly linked to inflammation. CD11b, is a biomarker abundant on inflammatory cells, not restricted to monocytes/macrophages. In this study, we fabricated a probe named as (99m)Tc-MAG3-anti-CD11b for detecting inflamed atherosclerotic plaques with single photon emission computed tomography/computed tomography (SPECT/CT). The ApoE-knockout (ApoE(-/-)) mice were selected to establish animal models, with C57BL/6J mice used for control. A higher CD11b(+)-cell recruitment with higher CD11b expression and more serious whole-body inflammatory status were identified in ApoE(-/-) mice. The probe showed high in vitro affinity and specificity to the Raw-264.7 macrophages, as well as inflammatory cells infiltrated in atherosclerotic plaques, either in ex vivo fluorescent imaging or in in vivo micro-SPECT/CT imaging, which were confirmed by ex vivo planar gamma imaging, Oil-Red-O staining and CD11b-immunohistochemistry staining. A significant positive relationship was identified between the radioactivity intensity on SPECT/CT images and the CD11b expression in plaques. In summary, this study demonstrates the feasibility of anti-CD11b antibody mediated noninvasive SPECT/CT imaging of inflammatory leukocytes in murine atherosclerotic plaques. This imaging strategy can identify inflammation-rich plaques at risk for rupture and evaluate the effectiveness of inflammation-targeted therapies in atheroma.
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.|Shanghai Institute of Medical Imaging, Shanghai 200032, China.
authors.forename: Guobing
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.|Shanghai Institute of Medical Imaging, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.|Shanghai Institute of Medical Imaging, Shanghai 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.|Shanghai Institute of Medical Imaging, Shanghai 200032, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.|Shanghai Institute of Medical Imaging, Shanghai 200032, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.|Shanghai Institute of Medical Imaging, Shanghai 200032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.|Shanghai Institute of Medical Imaging, Shanghai 200032, China.
authors.forename: Yanzhao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.|Shanghai Institute of Medical Imaging, Shanghai 200032, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.|Shanghai Institute of Medical Imaging, Shanghai 200032, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Shi
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D039481:CD11b Antigen / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D000067996:RAW 264.7 Cells; D000072098:Single Photon Emission Computed Tomography Computed Tomography
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D039481:CD11b Antigen