Correlation of FAPI PET Uptake with Immunohistochemistry in Explanted Lungs from Patients with Advanced Interstitial Lung Disease.

Masatoshi Hotta, Grace Hyun J Kim, Vilasinee Rerkpichaisuth, Pang Yu Teng, Wesley R Armstrong, Giuseppe Carlucci, Magnus Dahlbom, Fereidoun Abtin, Shahrzad M Lari, Gregory A Fishbein, Johannes Czernin, Elizabeth R Volkmann, S Sam Weigt, Jeremie Calais
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Abstract

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 SUVmax and SUVmean showed a positive correlation with the immunohistochemical FAP expression score (SUVmax: r = 0.57, P = 0.001; SUVmean: 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.

晚期肺间质疾病患者移植肺中 FAPI PET 摄取与免疫组织化学的相关性
最近的研究表明,成纤维细胞活化蛋白(FAP)抑制剂(FAPI)PET 在间质性肺病(ILD)的预后和监测方面具有良好的效果。作为成功转化的第一步,我们的主要目的是通过免疫组化方法验证 FAPI PET 摄取情况,研究对象是接受 FAPI PET 扫描后进行肺移植的晚期 ILD 患者。方法:这是一项针对 ILD 患者的 68Ga-FAPI-46 PET 成像的单中心、开放标签、单臂、前瞻性探索性生物分布研究(NCT05365802)的初步分析。研究对象包括经高分辨率 CT 确认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中获取肺组织样本。另外,还从与 FAPI PET 活性区域相对应的肺部区域获取样本。用抗 FAP 抗体进行免疫组化染色。使用 QuPath 软件半自动测量 FAP 免疫组化阳性区域的百分比。病理样本区域的 SUV 值是通过 FAPI PET/CT 参照被取出肺部的大体图像测量的。斯皮尔曼相关系数检验用于评估每个标本中 FAPI PET 摄取与 FAP 免疫组化表达之间的关系。结果:纳入了四名在肺移植前接受 FAPI PET/CT 检查的晚期 ILD 患者。ILD类型分别为特发性肺纤维化(2例)、类风湿性关节炎相关ILD(1例)和非特异性间质性肺炎(1例)。CT显示的FAPI摄取主要在纤维化区域。对 3 名患者的 29 份手术病理样本进行了分析。FAP染色主要在成纤维细胞灶呈阳性。FAPI PET SUVmax 和 SUVmean 与免疫组化 FAP 表达评分呈正相关(SUVmax:r = 0.57,P = 0.001;SUVmean:r = 0.54,P = 0.002)。结论在这项对接受 FAPI PET 扫描后进行肺移植的患者进行的分析中,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 作为潜在的 ILD 影像生物标志物提供了依据。
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