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

• DOI: 10.2967/jnumed.123.266910
• Publication Date: 2024-03-28T18:55:28Z
• Authors: Xiuli Zhang; Gyu Seong Heo; Alexandria Li; Divangana Lahad; Lisa Detering; Joan Tao; Xuefeng Gao; Xiaohui Zhang; Hannah Luehmann; Deborah Sultan; Lanlan Lou; Rajiu Venkatesan; Ran Li; Jie Zheng; Junedh Amrute; Chieh-Yu Lin; Benjamin J. Kopecky; Robert J. Gropler; Andrea Bredemeyer; Kory Lavine; Yongjian Liu
• Keywords: Biodistribution; CD163; Immunostaining

Tissue-resident macrophages are complementary to proinflammatory promote the progression of atherosclerosis. The noninvasive detection their presence and dynamic variation will be important understanding role in pathogenesis goal this study was develop a targeted PET radiotracer for imaging CD163-positive (CD163+) multiple mouse atherosclerosis models assess potential CD163 as biomarker humans. <b>Methods:</b> CD163-binding peptide identified using phage display conjugated with NODAGA chelator ⁶⁴Cu radiolabeling ([⁶⁴Cu]Cu-ICT-01). CD163-overexpressing U87 cells were used measure binding affinity [⁶⁴Cu]Cu-ICT-01. Biodistribution studies performed on wild-type C57BL/6 mice at time points after tail vein injection. sensitivity specificity [⁶⁴Cu]Cu-ICT-01 CD163+ upregulated surface atherosclerotic plaques assessed models. Immunostaining, flow cytometry, single-cell RNA sequencing characterize expression tissue-resident macrophages. Human carotid resident test <b>Results:</b> showed high cells. biodistribution rapid blood renal clearance low retention all major organs 1, 2, 4 h In an ApoE^−/− model, demonstrated sensitive specific capability tracking lesions; these findings further confirmed Ldlr^−/− PCSK9 Immunostaining elevated across plaques. Flow cytometry tissue characterization lesions, ex vivo autoradiography revealed human CD163. <b>Conclusion:</b> This work reported development indicated vulnerable warrant investigation translational settings.