Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074, Singapore.
Theranostics. 2023 May 15;13(9):2979-2992. doi: 10.7150/thno.86007. eCollection 2023.
Early discovery, accurate diagnosis, and staging of lung cancer is essential for patients to receive appropriate treatment. PET/CT has become increasingly recognized as a valuable imaging modality for these patients, but there remains room for improvement in PET tracers. We aimed to evaluate the feasibility of using [Ga]Ga-FAPI-RGD, a dual-targeting heterodimeric PET tracer that recognizes both fibroblast activation protein (FAP) and integrin αβ for detecting lung neoplasms, by comparing it with [F]FDG and single-targeting tracers [Ga]Ga-RGD and [Ga]Ga-FAPI. This was a pilot exploratory study of patients with suspected lung malignancies. All 51 participants underwent [Ga]Ga-FAPI-RGD PET/CT, of which: 9 participants received dynamic scans, 44 participants also underwent [F]FDG PET/CT scan within two weeks, 9 participants underwent [Ga]Ga-FAPI PET/CT scan and 10 participants underwent [Ga]Ga-RGD PET/CT scan. The final diagnosis was made based on histopathological analyses and clinical follow-up reports. Among those who underwent dynamic scans, the uptake of pulmonary lesions increased over time. The optimal timepoint for a PET/CT scan was identified to be 2 h post-injection. [Ga]Ga-FAPI-RGD had a higher detection rate of primary lesions than [F]FDG (91.4% 77.1%, < 0.05), higher tumor uptake (SUVmax, 6.9 ± 5.3 5.3 ± 5.4, < 0.001) and higher tumor-to-background ratio (10.0 ± 8.4 9.0 ± 9.1, < 0.05), demonstrated better accuracy in mediastinal lymph node evaluation (99.7% 90.9%, < 0.001), and identified more metastases (254 220). There was also a significant difference between the uptake of [Ga]Ga-FAPI-RGD and [Ga]Ga-RGD of primary lesions (SUVmax, 5.8 ± 4.4 2.3 ± 1.3, < 0.001). In our small scale cohort study, [Ga]Ga-FAPI-RGD PET/CT gave a higher primary tumor detection rate, higher tracer uptake, and improved detection of metastases compared with [F]FDG PET/CT, and [Ga]Ga-FAPI-RGD also had advantages over [Ga]Ga-RGD and was non-inferior to [Ga]Ga-FAPI. We thus provide proof-of-concept for using [Ga]Ga-FAPI-RGD PET/CT for diagnosing lung cancer. With the stated advantages, the dual-targeting FAPI-RGD should also be explored for therapeutic use in future studies.
早期发现、准确诊断和分期肺癌对于患者接受适当的治疗至关重要。PET/CT 已越来越被认为是这些患者有价值的成像方式，但 PET 示踪剂仍有改进的空间。我们旨在通过比较[Ga]Ga-FAPI-RGD 与[F]FDG 和单靶点示踪剂[Ga]Ga-RGD 和[Ga]Ga-FAPI 来评估其检测肺肿瘤的可行性，[Ga]Ga-FAPI-RGD 是一种识别成纤维细胞激活蛋白（FAP）和整合素αβ的双靶向杂二聚体 PET 示踪剂。这是一项疑似肺癌恶性肿瘤患者的探索性研究。所有 51 名参与者均接受了[Ga]Ga-FAPI-RGD PET/CT 检查，其中：9 名参与者进行了动态扫描，44 名参与者在两周内还进行了[F]FDG PET/CT 扫描，9 名参与者进行了[Ga]Ga-FAPI PET/CT 扫描，10 名参与者进行了[Ga]Ga-RGD PET/CT 扫描。最终诊断基于组织病理学分析和临床随访报告。在进行动态扫描的参与者中，肺部病变的摄取随时间增加。确定 PET/CT 扫描的最佳时间点为注射后 2 小时。[Ga]Ga-FAPI-RGD 对原发性病变的检出率高于[F]FDG（91.4%比 77.1%，<0.05），肿瘤摄取更高（SUVmax，6.9 ± 5.3 比 5.3 ± 5.4，<0.001），肿瘤与背景比更高（10.0 ± 8.4 比 9.0 ± 9.1，<0.05），在纵隔淋巴结评估中具有更高的准确性（99.7%比 90.9%，<0.001），并发现更多转移灶（254 个比 220 个）。原发性病变的[Ga]Ga-FAPI-RGD 和[Ga]Ga-RGD 摄取之间也存在显著差异（SUVmax，5.8 ± 4.4 比 2.3 ± 1.3，<0.001）。在我们的小样本队列研究中，[Ga]Ga-FAPI-RGD PET/CT 对原发性肿瘤的检出率、示踪剂摄取均高于[F]FDG PET/CT，且对转移灶的检测也优于[Ga]Ga-FAPI-RGD，与[Ga]Ga-FAPI 相比无差异。因此，我们为使用[Ga]Ga-FAPI-RGD PET/CT 诊断肺癌提供了概念验证。鉴于其所述优势，在未来的研究中，应探索双靶向 FAPI-RGD 用于治疗。
