Jiao Jian, Hu Biao, Mou Tiantian, Li Quan, Tian Yi, Zhang Nan, Zhang Ying, Yun Mingkai, Nan Nan, Tian Jing, Yu Wei, Mi Hongzhi, Dong Wei, Song Xiantao
Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Mol Pharm. 2024 Jul 1;21(7):3623-3633. doi: 10.1021/acs.molpharmaceut.4c00344. Epub 2024 May 31.
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, F-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. F-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 aorta PET imaging was also performed at 24 weeks. The SUV and SUV of F-FDPA were measured on the target organ, and the target-to-background ratio (TBR) was calculated as SUV/SUV. 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 TBR of F-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 F-FDPA uptake. This indicates a correlation between F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.
易损动脉粥样硬化斑块（VAP）内活化巨噬细胞诱导的炎症是斑块破裂的重要危险因素。转运体蛋白（TSPO）在活化巨噬细胞中高度表达。本研究调查了TSPO放射性示踪剂F-FDPA在检测兔VAP和定量斑块炎症方面的有效性。18只新西兰兔分为3组：假手术组A、VAP模型组B和依洛尤单抗治疗组C。所有组在第12、16和24周进行F-FDPA PET/CTA成像。在第24周对腹主动脉进行光学相干断层扫描（OCT）。通过OCT图像定义VAP，并在第24周也进行主动脉PET成像。在靶器官上测量F-FDPA的SUV和SUV，并计算靶本比（TBR）为SUV/SUV。对分离的腹主动脉动脉段进行HE染色、CD68和TSPO免疫荧光染色以及TSPO Western印迹分析。结果显示，在第24周时，B组F-FDPA的斑块TBR显著高于A组和C组。CD68和TSPO的免疫荧光染色以及Western印迹证实了B组相应区域巨噬细胞和TSPO表达增加。HE染色显示在F-FDPA摄取高的区域脂质核心、多个泡沫细胞和炎性细胞浸润增加。这表明F-FDPA摄取、炎症严重程度与VAP之间存在相关性。靶向TSPO的示踪剂F-FDPA在动脉粥样硬化斑块富含巨噬细胞的区域显示出特异性摄取，使其成为评估VAP炎症的有价值工具。
