Dual targeting PET tracer [ 68 Ga]Ga-FAPI-RGD in patients with lung neoplasms: a pilot exploratory study

• Published in: Theranostics Vol. 13; no. 9; pp. 2979 - 2992
• Main Authors: Wang, Rongxi, Jakobsson, Vivianne, Wang, Jiarou, Zhao, Tianzhi, Peng, Xingtong, Li, Bowen, Xue, Jianchao, Liang, Naixin, Zhu, Zhaohui, Chen, Xiaoyuan, Zhang, Jingjing
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher 01.01.2023
• Subjects: Cohort Studies; Fluorodeoxyglucose F18; Gallium Radioisotopes; Humans; Lung Neoplasms - diagnostic imaging; Oligopeptides; Positron Emission Tomography Computed Tomography; Quinolines; Research Paper; Integrin αvβ3; [18F]FDG; FAP; Lung neoplasm; [68Ga]Ga-FAPI-RGD
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.86007

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 α β 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.