Yuchun Wei1,2, Jinsong Zheng3, Li Ma3, Xiaoli Liu1,2, Shengnan Xu4, Shijie Wang4, Jinli Pei4, Kai Cheng5,6, Shuanghu Yuan7,8, Jinming Yu9,10. 1. Department of Radiology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. 2. Department of Radiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. 3. Department of PET/CT Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. 4. Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China. 5. Department of PET/CT Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. kcsdut@163.com. 6. Department of PET/CT, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong, 250117, Jinan, China. kcsdut@163.com. 7. Department of Radiology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. yuanshuanghu@sina.com. 8. Department of Radiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. yuanshuanghu@sina.com. 9. Department of Radiology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. sdyujinming@126.com. 10. Department of Radiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. sdyujinming@126.com.
Abstract
PURPOSE: In this pilot study, we developed a new tracer, [18F]AlF-labeled FAPI-04 chelated with NOTA, denoted as [18F]AlF-NOTA-FAPI-04, and tested the specificity, biodistribution, and clinical application for PET/computed tomography (CT) imaging of various types of cancers in patients. METHODS: In vitro binding specificity of FAPI-04 to FAP was verified in U87 cells confocal of a fluorescence-labeled variant. In vivo imaging, competition, and dynamic scanning analyses were conducted to evaluate [18F]AlF-NOTA-FAPI-04 imaging in xenograft mouse model using small-animal PET/CT. The application of [18F]AlF-NOTA-FAPI-04 was analyzed by imaging different types of cancers in patients. RESULTS: Both in vitro and in vivo results showed high binding specificity of FAPI-04 to FAP. High intratumoral uptake and fast body clearance of the tracer were observed in the xenograft mouse model and cancer patients. High-contrast images and negligible radiation exposure to normal tissue were observed on [18F]AlF-NOTA-FAPI-04 PET/CT in 28 patients with 8 different types of cancers. Five of 28 patients underwent PET/CT scanning at 1 h, 2 h, and 4 h after intravenous injection of [18F]AlF-NOTA-FAPI-04. Seven patients with advanced lung cancer underwent dual-tracer imaging, and 44 and 37 metastatic lesions were detected by [18F]AlF-NOTA-FAPI-04 PET/CT and [18F]F-FDG PET/CT, respectively. Overall, 80.0% of metastatic lesions was identified by both [18F]AlF-NOTA-FAPI-04 and 18F-FDG, 17.8% by [18F]AlF-NOTA-FAPI-04 PET/CT only, and 2.2% by [18F]FDG PET/CT only. CONCLUSION: [18F]AlF-NOTA-FAPI-04 offers high specificity as a tracer for FAP imaging and allows fast imaging with high contrast in tumors. [18F]AlF-NOTA-FAPI-04 is better at identifying metastatic lesions in patients with advanced lung cancer than [18F]FDG, and its use may facilitate tumor staging.
PURPOSE: In this pilot study, we developed a new tracer, [18F]AlF-labeled FAPI-04 chelated with NOTA, denoted as [18F]AlF-NOTA-FAPI-04, and tested the specificity, biodistribution, and clinical application for PET/computed tomography (CT) imaging of various types of cancers in patients. METHODS: In vitro binding specificity of FAPI-04 to FAP was verified in U87 cells confocal of a fluorescence-labeled variant. In vivo imaging, competition, and dynamic scanning analyses were conducted to evaluate [18F]AlF-NOTA-FAPI-04 imaging in xenograft mouse model using small-animal PET/CT. The application of [18F]AlF-NOTA-FAPI-04 was analyzed by imaging different types of cancers in patients. RESULTS: Both in vitro and in vivo results showed high binding specificity of FAPI-04 to FAP. High intratumoral uptake and fast body clearance of the tracer were observed in the xenograft mouse model and cancer patients. High-contrast images and negligible radiation exposure to normal tissue were observed on [18F]AlF-NOTA-FAPI-04 PET/CT in 28 patients with 8 different types of cancers. Five of 28 patients underwent PET/CT scanning at 1 h, 2 h, and 4 h after intravenous injection of [18F]AlF-NOTA-FAPI-04. Seven patients with advanced lung cancer underwent dual-tracer imaging, and 44 and 37 metastatic lesions were detected by [18F]AlF-NOTA-FAPI-04 PET/CT and [18F]F-FDG PET/CT, respectively. Overall, 80.0% of metastatic lesions was identified by both [18F]AlF-NOTA-FAPI-04 and 18F-FDG, 17.8% by [18F]AlF-NOTA-FAPI-04 PET/CT only, and 2.2% by [18F]FDG PET/CT only. CONCLUSION: [18F]AlF-NOTA-FAPI-04 offers high specificity as a tracer for FAP imaging and allows fast imaging with high contrast in tumors. [18F]AlF-NOTA-FAPI-04 is better at identifying metastatic lesions in patients with advanced lung cancer than [18F]FDG, and its use may facilitate tumor staging.
Authors: Yuka Otaki; Serge D Van Kriekinge; Chih-Chun Wei; Paul Kavanagh; Ananya Singh; Tejas Parekh; Marcelo Di Carli; Jamshid Maddahi; Arkadiusz Sitek; Christopher Buckley; Daniel S Berman; Piotr J Slomka Journal: Eur J Nucl Med Mol Imaging Date: 2021-12-30 Impact factor: 10.057
Authors: Lukas Greifenstein; Carsten S Kramer; Euy Sung Moon; Frank Rösch; Andre Klega; Christian Landvogt; Corinna Müller; Richard P Baum Journal: Pharmaceuticals (Basel) Date: 2022-08-14