Chronic hypertension leads to injury and fibrosis in major organs. Fibroblast activation protein (FAP) is one of key molecules in tissue fibrosis, and ⁶⁸Ga-labeled FAP inhibitor-46 (FAPI46) PET is a recently developed method for evaluating FAP. The aim of this study was to evaluate FAP expression and fibrosis in a hypertension model and to test the feasibility of ⁶⁸Ga-FAPI46 PET in hypertension. Methods: Hypertension was induced in mice by angiotensin II infusion for 4 wk. ⁶⁸Ga-FAPI46 biodistribution studies and PET scanning were conducted at 1, 2, and 4 wk after hypertension modeling, and uptake in the major organs was measured. The FAP expression and fibrosis formation of the heart and kidney tissues were analyzed and compared with ⁶⁸Ga-FAPI46 uptake. Subgroups of the hypertension model underwent angiotensin receptor blocker administration and high-dose FAPI46 blocking, for comparison. As a preliminary human study, ⁶⁸Ga-FAPI46 PET images of lung cancer patients were analyzed and compared between hypertension and control groups. Results: Uptake of ⁶⁸Ga-FAPI46 in the heart and kidneys was significantly higher in the hypertension group than in the sham group as early as week 1 and decreased after week 2. The uptake was specifically blocked in the high-dose blocking study. Immunohistochemistry also revealed FAP expression in both heart and kidney tissues. However, overt fibrosis was observed in the heart, whereas it was absent from the kidneys. The angiotensin receptor blocker–treated group showed lower uptake in the heart and kidneys than did the hypertension group. In the pilot human study, renal uptake of ⁶⁸Ga-FAPI46 significantly differed between the hypertension and control groups. Conclusion: In hypertension, FAP expression is increased in the heart and kidneys from the early phases and decreases over time. FAP expression appears to represent fibrosis activity preceding or underlying fibrotic tissue formation. ⁶⁸Ga-FAPI46 PET has potential as an effective imaging method for evaluating FAP expression in progressive fibrosis by hypertension.

慢性高血压导致主要器官损伤和纤维化。成纤维细胞活化蛋白 （FAP） 是组织纤维化的关键分子之一，⁶⁸Ga标记的 FAP 抑制剂-46 （FAPI46） PET 是最近开发的一种评估 FAP 的方法。本研究的目的是评估高血压模型中 FAP 的表达和纤维化，并测试 ⁶⁸Ga-FAPI46 PET 在高血压中的可行性。方法：通过输注血管紧张素 II 诱导小鼠高血压 4 w.高血压建模后 1 、 2 和 4 wk 进行 ⁶⁸Ga-FAPI46 生物分布研究和 PET 扫描，并测量主要器官的摄取。分析心脏和肾脏组织的 FAP 表达和纤维化形成，并与 ⁶⁸个 Ga-FAPI46 摄取进行比较。高血压模型的亚组接受血管紧张素受体阻滞剂给药和大剂量 FAPI46 阻断，以进行比较。作为一项初步的人体研究，分析了肺癌患者的 ⁶⁸张 Ga-FAPI46 PET 图像，并在高血压组和对照组之间进行了比较。结果：高血压组心脏和肾脏中 ⁶⁸Ga-FAPI46 的摄取率早在第 1 周就显著高于假手术组，第 2 周后下降。在高剂量阻断研究中，摄取被特别阻断。免疫组化还揭示了 FAP 在心脏和肾脏组织中的表达。然而，在心脏中观察到明显的纤维化，而在肾脏中则不存在。血管紧张素受体阻滞剂治疗组的心脏和肾脏摄取率低于高血压组。 在人体试点研究中，高血压组和对照组之间 ⁶⁸Ga-FAPI46 的肾脏摄取量存在显著差异。结论：在高血压中，FAP 在心脏和肾脏中的表达从早期开始增加，并随着时间的推移而降低。FAP 表达似乎代表纤维化组织形成之前或潜在的纤维化活动。⁶⁸Ga-FAPI46 PET 有可能成为评估高血压进行性纤维化中 FAP 表达的有效成像方法。