免疫检查点抑制剂（ICI）的使用会导致癌症患者出现免疫相关的不良事件，例如加速动脉粥样硬化。在参与动脉粥样硬化的免疫细胞中，CCR2（CC 基序趋化因子受体 2 阳性）促炎巨噬细胞的作用已得到充分证明。然而，目前还没有无创方法来确定 ICI 治疗后这些细胞在体内的变化，并探索免疫相关不良事件的潜在机制。在此，我们的目标是使用CCR2（CC基序趋化因子受体2）靶向放射性示踪剂和正电子发射断层扫描（PET）来评估小鼠动脉粥样硬化模型中ICI治疗引起的炎症反应加剧，并探讨免疫相关不良事件的机制。用 ICI、抗 PD1（程序性细胞死亡蛋白 1）抗体治疗 Apoe-/- 小鼠和 Ldlr-/- 小鼠，并与注射同种型对照 IgG 或盐水的小鼠进行比较。放射性示踪剂 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-ECL1i（细胞外环 1 反）用于 CCR2 巨噬细胞的 PET 成像。收集动脉粥样硬化动脉进行分子表征。CCR2 PET 显示，与对照组相比，接受抗 PD1 治疗的 Apoe-/- 和 Ldlr-/- 小鼠的放射性示踪剂摄取量显着更高。通过免疫染色和流式细胞术证实了 Apoe-/- 和 Ldlr-/- 小鼠中 CCR2 细胞表达的增加。单细胞 RNA 测序显示骨髓细胞中 CCR2 表达升高。从机制上讲，IFNγ（干扰素γ）对于抗PD1治疗后炎症加重和动脉粥样硬化斑块进展至关重要。1,4,7,10-tetraazacyclododecane-1,4可以无创地检测抗PD1治疗引发的加速动脉粥样硬化斑块炎症,7,10-四乙酸-ECL1i PET。斑块炎症加剧具有时间和剂量依赖性，并且主要由 IFNγ 信号传导介导。这项研究值得进一步研究 CCR2 PET 作为一种非侵入性方法来可视化动脉粥样硬化斑块炎症并探索 ICI 治疗后的潜在机制。

Immune checkpoint inhibitor (ICI) usage has resulted in immune-related adverse events in patients with cancer, such as accelerated atherosclerosis. Of immune cells involved in atherosclerosis, the role of CCR2+ (CC motif chemokine receptor 2-positive) proinflammatory macrophages is well documented. However, there is no noninvasive approach to determine the changes of these cells in vivo following ICI treatment and explore the underlying mechanisms of immune-related adverse events. Herein, we aim to use a CCR2 (CC motif chemokine receptor 2)-targeted radiotracer and positron emission tomography (PET) to assess the aggravated inflammatory response caused by ICI treatment in mouse atherosclerosis models and explore the mechanism of immune-related adverse events.Apoe-/- mice and Ldlr-/- mice were treated with an ICI, anti-PD1 (programmed cell death protein 1) antibody, and compared with those injected with either isotype control IgG or saline. The radiotracer 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-ECL1i (extracellular loop 1 inverso) was used for PET imaging of CCR2+ macrophages. Atherosclerotic arteries were collected for molecular characterization.CCR2 PET revealed significantly higher radiotracer uptake in both Apoe-/- and Ldlr-/- mice treated with anti-PD1 compared with the control groups. The increased expression of CCR2+ cells in Apoe-/- and Ldlr-/- mice was confirmed by immunostaining and flow cytometry. Single-cell RNA sequencing revealed elevated expression of CCR2 in myeloid cells. Mechanistically, IFNγ (interferon gamma) was essential for aggravated inflammation and atherosclerotic plaque progression following anti-PD1 treatment.Accelerated atherosclerotic plaque inflammation triggered by anti-PD1 treatment can be noninvasively detected by 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-ECL1i PET. Aggravated plaque inflammation is time- and dose-dependent and predominately mediated by IFNγ signaling. This study warrants further investigation of CCR2 PET as a noninvasive approach to visualize atherosclerotic plaque inflammation and explore the underlying mechanism following ICI treatment.