Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
J Nucl Med. 2021 Jan;62(1):111-114. doi: 10.2967/jnumed.120.244673. Epub 2020 May 22.
Proinflammatory macrophages are important mediators of inflammation after myocardial infarction and of allograft injury after heart transplantation. The aim of this study was to image the recruitment of proinflammatory chemokine receptor 2-positive (CCR2+) cells in multiple heart injury models. Cu-DOTA-extracellular loop 1 inverso (ECL1i) PET was used to image CCR2+ monocytes and macrophages in a heart transplantation mouse model. Flow cytometry was performed to characterize CCR2+ cells. Autoradiography on a human heart specimen was conducted to confirm binding specificity. Cu- and Ga-DOTA-ECL1i were compared in an ischemia-reperfusion injury mouse model. Cu-DOTA-ECL1i showed sensitive and specific detection of CCR2+ cells in all tested mouse models, with efficacy comparable to that of Ga-DOTA-ECL1i. Flow cytometry demonstrated specific expression of CCR2 on monocytes and macrophages. The tracer binds to human CCR2. This work establishes the utility of Cu-DOTA-ECL1i to image CCR2+ monocytes and macrophages in mouse models and provides the requisite preclinical information to translate the targeted clinical-grade CCR2 imaging probe for clinical investigation of heart diseases.
促炎性巨噬细胞是心肌梗死后炎症和心脏移植后同种异体损伤的重要介质。本研究旨在对多种心脏损伤模型中促炎性趋化因子受体 2 阳性（CCR2+）细胞的募集进行成像。Cu-DOTA-外显子 1 反向（ECL1i）PET 用于在心脏移植小鼠模型中对 CCR2+单核细胞和巨噬细胞进行成像。通过流式细胞术对 CCR2+细胞进行了特征分析。对人体心脏标本进行放射自显影以确认结合特异性。在缺血再灌注损伤小鼠模型中比较了 Cu 和 Ga-DOTA-ECL1i。Cu-DOTA-ECL1i 在所有测试的小鼠模型中均能灵敏且特异性地检测 CCR2+细胞，其功效可与 Ga-DOTA-ECL1i 相媲美。流式细胞术表明单核细胞和巨噬细胞上特异性表达 CCR2。该示踪剂与人类 CCR2 结合。这项工作确立了 Cu-DOTA-ECL1i 在小鼠模型中对 CCR2+单核细胞和巨噬细胞进行成像的实用性，并提供了必要的临床前信息，以便将靶向临床级 CCR2 成像探针转化为心脏病的临床研究。
