Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of ⁶⁸Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis–associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUV_max and SUV_mean showed a positive correlation with the immunohistochemical FAP expression score (SUV_max: r = 0.57, P = 0.001; SUV_mean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.

最近的研究表明，成纤维细胞活化蛋白 （FAP） 抑制剂 （FAPI） PET 在预测和监测间质性肺疾病 （ILD） 方面取得了有希望的结果。作为成功翻译的第一步，我们的主要目标是通过 FAPI PET 扫描后接受肺移植的晚期 ILD 患者通过免疫组化验证 FAPI PET 摄取。方法： 这是对 ⁶⁸ 人的单中心、开放标签、单臂、前瞻性探索性生物分布研究的初步分析ILD 患者的 Ga-FAPI-46 PET 成像 （NCT05365802）。纳入经高分辨率 CT 确诊并计划进行肺移植的 ILD 患者。从每个肺叶的中央和外周肺实质获得外植肺的组织样本。从对应于 FAPI PET 活性区域的肺部区域获得额外的样本。用抗 FAP 抗体进行免疫组织化学染色。使用 QuPath 软件半自动测量 FAP 免疫组化阳性面积的百分比。通过参考外植肺的大体照片图，在 FAPI PET/CT 上测量病理样本区域的 SUV。采用 Spearman 相关系数检验评估每个标本中 FAPI PET 摄取与 FAP 免疫组化表达之间的关系。结果：纳入 4 例在肺移植前行 FAPI PET/CT 的晚期 ILD 患者。ILD 的类型为特发性肺纤维化 （n = 2）、类风湿性关节炎相关 ILD （n = 1） 和非特异性间质性肺炎 （n = 1）。FAPI 摄取主要在 CT 上的纤维化区域可见。 分析了 3 例患者的 29 例手术病理样本。FAP 染色在成纤维细胞病灶中主要为阳性。FAPI PET_{SUV max} 和 SUV_平均值与免疫组织化学 FAP 表达评分呈正相关 （SUV_max： r = 0.57，P = 0.001; SUV_平均值：r = 0.54，P = 0.002）。 结论：在 FAPI PET 扫描后接受肺移植的患者中进行的这项分析中，FAPI PET 摄取与 FAP 免疫组化呈正相关。这些发现为进一步研究 FAPI PET 作为 ILD 的潜在影像生物标志物提供了理论依据。