Abstract：
Inflammation induced by activated macrophages within vulnerable atherosclerotic plaques (VAPs) constitutes a significant risk factor for plaque rupture. Translocator protein (TSPO) is highly expressed in activated macrophages. This study investigated the effectiveness of TSPO radiotracers, 18F-FDPA, in detecting VAPs and quantifying plaque inflammation in rabbits. 18 New Zealand rabbits were divided into 3 groups: sham group A, VAP model group B, and evolocumab treatment group C. 18F-FDPA PET/CTA imaging was performed at 12, 16, and 24 weeks in all groups. Optical coherence tomography (OCT) was performed on the abdominal aorta at 24 weeks. The VAP was defined through OCT images, and ex vivo aorta PET imaging was also performed at 24 weeks. The SUVmax and SUVmean of 18F-FDPA were measured on the target organ, and the target-to-background ratio (TBRmax) was calculated as SUVmax/SUVblood pool. The arterial sections of the isolated abdominal aorta were analyzed by HE staining, CD68 and TSPO immunofluorescence staining, and TSPO Western blot. The results showed that at 24 weeks, the plaque TBRmax of 18F-FDPA in group B was significantly higher than in groups A and C. Immunofluorescence staining of CD68 and TSPO, as well as Western blot, confirmed the increased expression of macrophages and TSPO in the corresponding regions of group B. HE staining revealed an increased presence of the lipid core, multiple foam cells, and inflammatory cell infiltration in the area with high 18F-FDPA uptake. This indicates a correlation between 18F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.
摘要：
在易损的动脉粥样硬化斑块(VAP)内由活化的巨噬细胞诱导的炎症构成斑块破裂的重要危险因素。转运蛋白（TSPO）在活化的巨噬细胞中高度表达。这项研究调查了TSPO放射性示踪剂的有效性，18F-FDPA,在检测VAPs和量化兔斑块炎症中。18只新西兰大白兔分为3组：假手术组A、VAP模型B组,和evolocumab治疗组C.18F-FDPAPET/CTA成像在所有组均在12、16和24周进行。24周时在腹主动脉上进行光学相干断层扫描（OCT）。通过OCT图像确定VAP,在24周时还进行了离体主动脉PET成像。在靶器官上测量18F-FDPA的SUVmax和SUVmean，目标背景比(TBRmax)计算为SUVmax/SUV血池。分离的腹主动脉的动脉切片通过HE染色进行分析。CD68和TSPO免疫荧光染色，和TSPO蛋白质印迹。结果显示，在24周时，B组18F-FDPA斑块TBRmax明显高于A、C组。以及蛋白质印迹，证实巨噬细胞和TSPO在B组相应区域的表达增加。HE染色显示脂质核心的存在增加，多个泡沫细胞，18F-FDPA高摄取区域的炎性细胞浸润。这表明18F-FDPA摄取之间的相关性，炎症严重程度，和VAP。TSPO靶向示踪剂18F-FDPA在动脉粥样硬化斑块的富含巨噬细胞的区域显示特异性摄取,使其成为评估VAP炎症的有价值的工具。
