Translocator Protein 18 kDa Tracer 18F-FDPA PET/CTA Imaging for the Evaluation of Inflammation in Vulnerable Plaques

转运蛋白 炎症 正电子发射断层摄影术 分子成像 示踪剂 Pet成像 核医学 化学 医学 内科学 生物 核物理学 物理 生物技术 体内 神经炎症
作者
Jian Jiao,Biao Hu,Tiantian Mou,Quan Li,Yi Tian,Nan Zhang,Ying Zhang,Mingkai Yun,Nan Nan,Jing Tian,Wei Yu,Hongzhi Mi,Wei Dong,Xiantao Song
出处
期刊:Molecular Pharmaceutics [American Chemical Society]
卷期号:21 (7): 3623-3633 被引量:6
标识
DOI:10.1021/acs.molpharmaceut.4c00344
摘要

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, 18 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. 18 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 ex vivo aorta PET imaging was also performed at 24 weeks. The SUV max and SUV mean of 18 F-FDPA were measured on the target organ, and the target-to-background ratio (TBR max ) was calculated as SUV max /SUV blood 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 TBR max of 18 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 18 F-FDPA uptake. This indicates a correlation between 18 F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18 F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.
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