99mTc-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)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.