RT Journal Article SR Electronic T1 Exploring Macrophage Dynamics in Myocardial Infarction Through CCR2 and CD163 PET Imaging JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 242604 OP 242604 VO 65 IS supplement 2 A1 Venkatesan, Rajiu A1 Heo, Gyu Seong A1 Luehmann, Hannah A1 Lahad, Divangana A1 Liu, Yongjian YR 2024 UL http://jnm.snmjournals.org/content/65/supplement_2/242604.abstract AB 242604 Introduction: Macrophages exhibit remarkable plasticity, responding to tissue-specific signals and participating in diverse functions, including host defense, tissue repair, and cancer development. The heterogeneity and plasticity of macrophages are evident in how the microenvironment shapes their phenotype and functional identity, ensuring ongoing adaptation to the environment. The goal of this study is to interrogate CCR2 and CD163 PET signals to localize the temporal-spatial distribution of M1 and M2 macrophage subtypes in vivo and validate their relationship in animal inflammation models.Methods: Newly developed CCR2 and CD163 tracers were both radiolabeled with 68Ga and employed to determine the dynamic changes in M1 and M2 macrophage subsets through serial PET imaging, histopathological and immunostaining analyses, flow cytometry, and autoradiography studies using a post-MI mouse model with ischemia-reperfusion injury (acute inflammation) model. Results: [68Ga]-DOTA-ECL1i and [68Ga]-NODAGA-ICT-01 PET imaging were performed in a mouse model of ischemia-reperfusion injury-induced myocardial infarction. [18F]-FDG identified the infarct at day 3 post MI, while day 4 CCR2 PET showed intensive tracer uptake at the infarct zone, gradually decreasing during remodeling. CD163 PET signals were observed in the remote area, increasing from day 5 to day 13 and stabilizing until day 25. This study provides novel insights into the dynamic changes of macrophage subsets post MI, emphasizing the significance of PET imaging as a non-invasive tool for tracking macrophages in vivo and gaining a deeper understanding of their role in injury and remodeling processes.Conclusions: Our CCR2 and CD163 pair imaging demonstrated the dynamic variations of CCR2+ M1 and CD163+ M2 macrophages throughout the initiation, promotion, and resolution phases of inflammation. Tissue characterization robustly supports PET data on CCR2 and CD163 protein expression and immune cell profiles.