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Theranostics 2023; 13(9):2979-2992. doi:10.7150/thno.86007 This issue Cite

Research Paper

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

Rongxi Wang¹, Vivianne Jakobsson^2,3,4, Jiarou Wang¹, Tianzhi Zhao^2,3,4, Xingtong Peng⁵, Bowen Li^6,7, Jianchao Xue^6,7, Naixin Liang^6✉, Zhaohui Zhu^1✉, Xiaoyuan Chen^2,3,4,8✉, Jingjing Zhang^2,3,4✉

1. 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.
2. Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074, Singapore.
3. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
4. Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
5. Eight-Year Program of Clinical Medicine, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing 100730, China.
6. Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
7. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
8. Departments of Chemical and Biomolecular Engineering and Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117597, Singapore.

✉ Corresponding authors: Naixin Liang, MD, Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730, China. Email: pumchnelsoncom. Zhaohui Zhu, MD, Ph.D., Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing St, Dongcheng District, Beijing 100730, China. E-mail: 13611093752com. Xiaoyuan Chen, Ph.D., National University of Singapore, S9 Level 10, 4 Science Drive 2, Singapore 117544, Singapore. E-mail: chen.shawnedu.sg. Jingjing Zhang, MD, Ph.D., National University of Singapore, S9 Level 10, 4 Science Drive 2, Singapore 117544, Singapore. E-mail: j.zhangedu.sg. More

Abstract

Rationale: 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 [⁶⁸Ga]Ga-FAPI-RGD, a dual-targeting heterodimeric PET tracer that recognizes both fibroblast activation protein (FAP) and integrin α_vβ₃ for detecting lung neoplasms, by comparing it with [¹⁸F]FDG and single-targeting tracers [⁶⁸Ga]Ga-RGD and [⁶⁸Ga]Ga-FAPI.

Methods: This was a pilot exploratory study of patients with suspected lung malignancies. All 51 participants underwent [⁶⁸Ga]Ga-FAPI-RGD PET/CT, of which: 9 participants received dynamic scans, 44 participants also underwent [¹⁸F]FDG PET/CT scan within two weeks, 9 participants underwent [⁶⁸Ga]Ga-FAPI PET/CT scan and 10 participants underwent [⁶⁸Ga]Ga-RGD PET/CT scan. The final diagnosis was made based on histopathological analyses and clinical follow-up reports.

Results: 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. [⁶⁸Ga]Ga-FAPI-RGD had a higher detection rate of primary lesions than [¹⁸F]FDG (91.4% vs. 77.1%, p < 0.05), higher tumor uptake (SUVmax, 6.9 ± 5.3 vs. 5.3 ± 5.4, p < 0.001) and higher tumor-to-background ratio (10.0 ± 8.4 vs. 9.0 ± 9.1, p < 0.05), demonstrated better accuracy in mediastinal lymph node evaluation (99.7% vs. 90.9%, p < 0.001), and identified more metastases (254 vs. 220). There was also a significant difference between the uptake of [⁶⁸Ga]Ga-FAPI-RGD and [⁶⁸Ga]Ga-RGD of primary lesions (SUVmax, 5.8 ± 4.4 vs. 2.3 ± 1.3, p < 0.001).

Conclusion: In our small scale cohort study, [⁶⁸Ga]Ga-FAPI-RGD PET/CT gave a higher primary tumor detection rate, higher tracer uptake, and improved detection of metastases compared with [¹⁸F]FDG PET/CT, and [⁶⁸Ga]Ga-FAPI-RGD also had advantages over [⁶⁸Ga]Ga-RGD and was non-inferior to [⁶⁸Ga]Ga-FAPI. We thus provide proof-of-concept for using [⁶⁸Ga]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.

Keywords: [⁶⁸Ga]Ga-FAPI-RGD, [¹⁸F]FDG, Lung neoplasm, FAP, Integrin α_vβ₃

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