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(99m)Tc-labelled anti-CD11b SPECT/CT imaging allows detection of plaque destabilization tightly linked to inflammation

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)T...

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Detalles Bibliográficos
Autores principales: Liu, Guobing, Hu, Yan, Xiao, Jie, Li, Xiao, Li, Yanli, Tan, Hui, Zhao, Yanzhao, Cheng, Dengfeng, Shi, Hongcheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753504/
https://www.ncbi.nlm.nih.gov/pubmed/26877097
http://dx.doi.org/10.1038/srep20900
Descripción
Sumario: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-MAG(3)-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.