The Journal of Nuclear Medicine ( IF 9.1 ) Pub Date : 2025-01-01 , DOI: 10.2967/jnumed.124.268376 Peng Hou, Haiming Chen, Sihao Liang, Wenliang Guo, Ruiyue Zhao, Huailu Pan, Haimin Liu, Youcai Li, Jie Lv, Kaixiang Zhong, Miao Ke, Yimin Fu, Huizhen Zhong, Xinlu Wang, Cheng Hong
The purpose of this study was to investigate the feasibility of using 18F-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in assessing the fibrotic remodeling of the pulmonary artery (PA) and the right ventricle (RV) in pulmonary arterial hypertension (PAH). Methods: In a rat model of monocrotaline-induced PAH, rats were euthanized at different time points for tissue analysis (fibroblast activation protein immunofluorescence and Masson’s trichrome staining) after completing 18F-FAPI PET/CT and hemodynamic measurements. Thirty-eight PAH patients were enrolled to participate in 18F-FAPI PET/CT imaging, with right heart catheterization and echocardiography performed within 1 wk to assess pulmonary hemodynamics and cardiac function. Results: In the animal experiments, RV systolic pressure in monocrotaline rats increased from day 14 to day 21 after injection. 18F-FAPI uptake and fibroblast activation protein expression in the myocardium and lungs peaked on day 14 after injection. Collagen deposition in the RVs and peripheral PAs of monocrotaline rats progressively deteriorated from day 14 to day 21. In the human PAH study, 18F-FAPI PET/CT imaging identified varying degrees of 18F-FAPI uptake in the myocardium and proximal and distal PAs, correlating with clinical, RV function, and pulmonary hemodynamic parameters. Among the 5 follow-up patients who underwent a second 18F-FAPI PET/CT scan after 6 mo (range, 4–9 mo) of PAH-targeted therapy, 3 demonstrated reduced 18F-FAPI uptake, corresponding with clinical improvement. Conclusion: 18F-FAPI PET/CT imaging is feasible for visualizing the remodeling of the PA and the RV in PAH. Although it offers promise for assessing disease-related changes, its role in evaluating disease severity and monitoring therapeutic efficacy requires further investigation.
中文翻译:
靶向成纤维细胞活化蛋白用于肺动脉高压纤维化重塑的分子成像
本研究的目的是探讨使用 18种 F 标记的成纤维细胞活化蛋白抑制剂 (FAPI) PET/CT 评估肺动脉高压 (PAH) 中肺动脉 (PA) 和右心室 (RV) 纤维化重塑的可行性。方法:在野佛他碱诱导的 PAH 大鼠模型中,大鼠在完成 18F-FAPI PET/CT 和血流动力学测量后,在不同时间点对大鼠实施安乐死进行组织分析 (成纤维细胞活化蛋白免疫荧光和 Masson 三色染色)。入组 38 例 PAH 患者,参加 18例 F-FAPI PET/CT 成像,在 1 周内进行右心导管插入术和超声心动图检查,以评估肺血流动力学和心脏功能。结果:在动物实验中,野百合碱大鼠的 RV 收缩压从注射后第 14 天增加到第 21 天。18心肌和肺中 F-FAPI 摄取和成纤维细胞活化蛋白表达在注射后第 14 天达到峰值。从第 14 天到第 21 天,野百合碱大鼠 RVs 和外周 PAs 中的胶原沉积逐渐恶化。在人类 PAH 研究中,18F-FAPI PET/CT 成像确定了心肌以及近端和远端 PA 中不同程度的 18F-FAPI 摄取,与临床、RV 功能和肺血流动力学参数相关。在 PAH 靶向治疗 6 个月 (范围,4-9 个月) 后接受第二次 18F-FAPI PET/CT 扫描的 5 名随访患者中,3 名显示 18F-FAPI 摄取减少,与临床改善相对应。结论: 18F-FAPI PET/CT 成像可用于可视化 PAH 中 PA 和 RV 的重塑。 尽管它为评估疾病相关变化提供了希望,但其在评估疾病严重程度和监测治疗效果方面的作用需要进一步研究。