Strong 64Cu-TNP activity was observed in the (A) aortic root, (B) arch, and (C) carotid artery on fused PET/CT images at sites of atherosclerotic plaque burden in ApoE−/− mice. (D to F) Comparatively, scant 64Cu-TNP signal was identified in the same vascular beds of wild-type mice. Histology of respective vascular territories identified high plaque content in ApoE−/− mice but (I, K) not in wild-type controls (magnification: 400× for G and I, 200× for H and K; bar = 0.4 mm). Maximum intensity reconstruction of the 3-dimensional fused PET/CT data set demonstrates (L) focal 64Cu-TNP uptake (red) in the proximal thoracic aorta (blue) of ApoE−/− mice that is (M) absent in matched wild-type control animals. Reproduced, with permission, from Nahrendorf et al. (32). CT = computed tomography; PET = positron emission tomography; TNP = trimodality nanoparticle; 64Cu = copper Cu 64; other abbreviations as in Figures 1 and 2.