目的:动脉粥样硬化仍是心肌梗死和缺血性脑卒中的病理基础。早期和准确识别斑块对于改善动脉粥样硬化患者的临床预后至关重要。我们的研究旨在评估成纤维细胞活化蛋白抑制剂(FAPI)-04PET/CT在通过动脉粥样硬化的临床前兔模型识别斑块中的潜在价值。
方法:新西兰大白兔饲喂高脂饮食(HFD),并随机分为球囊损伤模型组,假手术组只有切口。进行超声检查以检测斑块,通过Al18F-NOTA-FAPI-04PET/CT测定FAPI-aid。比较病变的平均标准化摄取值(SUVmean),计算Al18F-NOTA-FAPI-04的生物分布和目标背景比(TBRs)。进行组织学染色以显示动脉斑块,和放射自显影(ARG)用于测量Al18F-NOTA-FAPI-04的体外强度。最后,FAP水平之间的相关性,斑块面积,评估SUV平均值和纤维帽厚度。
结果:建立兔颈动脉和腹部动脉粥样硬化模型。Al18F-NOTA-FAPI-04显示颈动脉斑块(SUVmean1.32±0.11)和腹部斑块(SUVmean0.73±0.13)的摄取高于相应的对照(SUVmean1.07±0.06;0.46±0.03)(P<0.05)。Al18F-NOTA-FAPI-04的生物分布分析揭示较大的斑块被较高的TBR描绘。病理染色显示动脉斑块的形成,和ARG染色在较大的斑块中表现出更高强度的Al18F-NOTA-FAPI-04。最后,发现斑块面积与FAP表达和SUVmean呈正相关,FAP表达与斑块的纤维帽厚度呈负相关。
结论:我们成功实现了兔动脉粥样硬化病变成纤维细胞活化的分子成像,提示Al18F-NOTA-FAPI-04PET/CT可能是识别斑块的潜在有价值的工具。
OBJECTIVE: Atherosclerosis remains the pathological basis of myocardial infarction and ischemic stroke. Early and accurate identification of plauqes is crucial to improve clinical outcomes of atherosclerosis patients. Our study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-04 PET/CT in identifying plaques via a preclinical rabbit model of atherosclerosis.
METHODS: New Zealand white rabbits were fed high-fat diet (HFD), and randomly divided into the model group injured by the balloon, and the sham group only with incisions. Ultrasound was performed to detect plaques, and FAPI-avid was determined through Al18F-NOTA-FAPI-04 PET/CT. Mean standardized uptake values (SUVmean) in lesions were compared, and biodistribution of Al18F-NOTA-FAPI-04 and target-to-background ratios (TBRs) were calculated. Histological staining was performed to display arterial plaques, and autoradiography (ARG) was employed to measure the in vitro intensity of Al18F-NOTA-FAPI-04. At last, the correlation among FAP levels, plaque area, SUVmean values and fibrous cap thickness was assessed.
RESULTS: The rabbit carotid and abdominal atherosclerosis model was established. Al18F-NOTA-FAPI-04 showed a higher uptake in carotid plaques (SUVmean 1.32 ± 0.11) and abdominal plaques (SUVmean 0.73 ± 0.13) compared to corresponding controls (SUVmean 1.07 ± 0.06; 0.46 ± 0.03) (P < 0.05). Biodistribution analysis of Al18F-NOTA-FAPI-04 revealed that the bigger plaques were delineated with higher TBRs. Pathological staining showed the formation of arterial plaques, and ARG staining exhibited a higher intensity of Al18F-NOTA-FAPI-04 in the bigger plaques. Lastly, plaque area was found to be positively correlated to FAP expression and SUVmean, while FAP expression was negatively correlated to fibrous cap thickness of plaques.
CONCLUSIONS: We successfully achieve molecular imaging of fibroblast activation in atherosclerotic lesions of rabbits, suggesting Al18F-NOTA-FAPI-04 PET/CT may be a potentially valuable tool to identify plaques.