Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany;
Department of Nuclear Medicine, University Hospital Mainz, Mainz, Germany.
J Nucl Med. 2024 Jun 3;65(6):872-879. doi: 10.2967/jnumed.123.267103.
PET using Ga-labeled fibroblast activation protein (FAP) inhibitors (FAPIs) holds high potential for diagnostic imaging of various malignancies, including lung cancer (LC). However, F-FDG PET is still the clinical gold standard for LC imaging. Several subtypes of LC, especially lepidic LC, are frequently F-FDG PET-negative, which markedly hampers the assessment of single pulmonary lesions suggestive of LC. Here, we evaluated the diagnostic potential of static and dynamic Ga-FAPI-46 PET in the F-FDG-negative pulmonary lesions of 19 patients who underwent surgery or biopsy for histologic diagnosis after PET imaging. For target validation, FAP expression in lepidic LC was confirmed by FAP immunohistochemistry. Hematoxylin and eosin staining and FAP immunohistochemistry of 24 tissue sections of lepidic LC from the local tissue bank were performed and analyzed visually. Clinically, 19 patients underwent static and dynamic Ga-FAPI-46 PET in addition to F-FDG PET based on individual clinical indications. Static PET data of both examinations were analyzed by determining SUV, SUV, and tumor-to-background ratio (TBR) against the blood pool, as well as relative parameters (Ga-FAPI-46 in relation toF-FDG), of histologically confirmed LC and benign lesions. Time-activity curves and dynamic parameters (time to peak, slope, , , , and ) were extracted from dynamic Ga-FAPI-46 PET data. The sensitivity and specificity of all parameters were analyzed by calculating receiver-operating-characteristic curves. FAP immunohistochemistry confirmed the presence of strongly FAP-positive cancer-associated fibroblasts in lepidic LC. LC showed markedly elevated Ga-FAPI-46 uptake, higher TBRs, and higher Ga-FAPI-46-to-F-FDG ratios for all parameters than did benign pulmonary lesions. Dynamic imaging analysis revealed differential time-activity curves for LC and benign pulmonary lesions: initially increasing time-activity curves with a decent slope were typical of LC, and steadily decreasing time-activity curve indicated benign pulmonary lesions, as was reflected by a significantly increased time to peak and significantly smaller absolute values of the slope for LC. Relative Ga-FAPI-46-to-F-FDG ratios regarding SUV and TBR showed the highest sensitivity and specificity for the discrimination of LC from benign pulmonary lesions. Ga-FAPI-46 PET is a powerful new tool for the assessment of single F-FDG-negative pulmonary lesions and may optimize patient stratification in this clinical setting.
使用 Ga 标记的成纤维细胞激活蛋白 (FAP) 抑制剂 (FAPIs) 的 PET 对包括肺癌 (LC) 在内的各种恶性肿瘤的诊断成像具有很高的潜力。然而，F-FDG PET 仍然是 LC 成像的临床金标准。LC 的一些亚型，特别是贴壁型 LC，通常 F-FDG PET 为阴性，这极大地阻碍了对疑似 LC 的单个肺部病变的评估。在这里，我们评估了静态和动态 Ga-FAPI-46 PET 在 19 名接受 PET 成像后手术或活检进行组织学诊断的 F-FDG 阴性肺部病变患者中的诊断潜力。为了验证靶标，通过 FAP 免疫组织化学证实贴壁型 LC 中的 FAP 表达。对当地组织库中 24 个贴壁型 LC 组织切片进行苏木精和伊红染色和 FAP 免疫组织化学分析，并进行视觉分析。临床上，根据个人临床指征，19 名患者除了 F-FDG PET 外，还进行了静态和动态 Ga-FAPI-46 PET。通过确定 SUV、SUV 和肿瘤与背景比 (TBR) 与血池，以及相对参数 (Ga-FAPI-46 与 F-FDG 相关)，对两种检查的静态 PET 数据进行分析，与组织学证实的 LC 和良性病变相关。从动态 Ga-FAPI-46 PET 数据中提取时间-活性曲线和动态参数 (达峰时间、斜率、 、 、 、和 )。通过计算受试者工作特征曲线分析所有参数的敏感性和特异性。FAP 免疫组织化学证实贴壁型 LC 中存在强烈的 FAP 阳性癌相关成纤维细胞。与良性肺病变相比，LC 的 Ga-FAPI-46 摄取明显升高，TBR 更高，Ga-FAPI-46 与 F-FDG 的比值更高。动态成像分析显示 LC 和良性肺病变的时间-活性曲线存在差异：LC 的初始增加斜率的时间-活性曲线是典型的，而逐渐减少的时间-活性曲线表明良性肺病变，这反映在 LC 的达峰时间显著增加和斜率的绝对值显著减小。关于 SUV 和 TBR 的相对 Ga-FAPI-46 与 F-FDG 的比值在区分 LC 和良性肺病变方面具有最高的敏感性和特异性。Ga-FAPI-46 PET 是一种评估单个 F-FDG 阴性肺部病变的强大新工具，可能会优化这种临床情况下的患者分层。
