Development of a CD163-Targeted PET Radiotracer That Images Resident Macrophages in Atherosclerosis

In vitro and in vivo characterization of [⁶⁴Cu]Cu-ICT-01. (A) Cell-binding assay in human U87 cells and mouse RAW 264.7 cells. (B) Biodistribution in WT C57BL/6 mice (n = 4/group). IC₅₀ = half-maximal inhibitory concentration.

PET/CT imaging and characterization of CD163+ macrophages in ApoE^−/− mice. (A) Representative PET/CT images of [⁶⁴Cu]Cu-ICT-01. (B) Quantification of uptake at aortic arches in WT and ApoE^−/− mice on HFD at various time points (n = 4–7/group). (C) Hematoxylin and eosin and immunofluorescence staining. (D) [⁶⁴Cu]Cu-ICT-01 autoradiography of aorta, spleen, and thymus. (E) Flow cytometry. (F) Single-cell RNA sequencing of macrophages collected from ApoE^−/− mouse aortas after 20 wk on HFD. Resident macrophage gene set score uses Folr2, Lyve1, and F13a1 (top) and gene expression density (bottom) for Cd163 in uniform manifold approximation and projection embedding. *P < 0.05. **P < 0.01. ***P < 0.001. ****P < 0.0001. DAPI = (4′,6-diamidino-2-phenylindole); H&E = hematoxylin and eosin; UMAP_1 = uniform manifold approximation and projection 1.

PET/CT imaging and characterization of CD163+ macrophages in PCSK9 mice. (A) Representative PET/CT images of [⁶⁴Cu]Cu-ICT-01 in PCSK9 mice. (B) Quantification of uptake at aortic arches at various time points on HFD (n = 4–8/group). ****P < 0.0001.