RT Journal Article SR Electronic T1 Ga-68-FAPI-46 labelling strategy for future clinical use in Taiwan JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 2831 OP 2831 VO 63 IS supplement 2 A1 Li, Ming-Hsin A1 Huang, Yu-Yi A1 Huang, Kuo-Cheng YR 2022 UL http://jnm.snmjournals.org/content/63/supplement_2/2831.abstract AB 2831 Introduction: Fibrous activation protein inhibitor (FAPI) as a potential imaging tracer to use in numerous kinds of solid tumors has been reported. The FAPI-46 was shown to be one of the best analogs with excellent tumor retention and high tumor-to-background ratio. According to the design of the structure, the DOTA was used as chelator in FAPI-46 for labelling radionuclides like gallium-68 for PET image or lutetium-177 radionuclide therapy. FAPI-46 has a great potential in diagnosis and treatment of recurrent colorectal cancer, and as a new candidate of theranostic agent in Sun Yat-Sen Cancer Center in Taiwan, where has established a radiopharmaceutical theranostic center that complies with the U.S. FDA GMP drug regulations and introduces the best drug labelling technology and automation equipment to welcome the era of precision medicine. This study tests low-FAPI-contain versus standard 50ug-FAPI-contain labelling parameters using technical grade FAPI-46 precursor and pharmaceutical grade Ge-68/Ga-68 generator for setting up our automated synthesizer (PharmaTracer, Eckert & Ziegler).Methods: Low-FAPI-contain method: dissolved FAPI-46 in water to make the solution concentration 1 mg/mL. Draw out FAPI-46 with 1.5, 2.0, 3.0, 7.0, 9.0ug and each added with 0.15 mL formulation buffer (Eckert & Ziegler EZ-102 reagent set). The Ga-68 eluents with 0.11(±15%) GBq were added into the into the reaction vial. Then incubated at 95 ℃ for 10 min. Standard 50ug-FAPI-contain method: dissolved 50 μg FAPI-46 in 2.2 mL formulation buffer as reaction vial. The Ga-68 eluent with 0.78 GBq was added into the reaction vial. Then incubated at 95 ℃ for 10 min. The Ga-68 was milked with 0.1N HCl from Ge-68/Ga-68 generator (from Eckert & Ziegler) then trapped with SCX cartridge and eluted by 0.6 mL NaCl/HCl (Eckert & Ziegler).Radiochemical purity was analyzed by thin layer chromatography (TLC) and high pressure liquid chromatography (HPLC). The 0.05 M citric buffer pH4.0 used as mobile phase for TLC. The Xselect HSS T3 column (4.6 mm x 250 mm) was used and eluted with a linear gradient from 10 to 50% acetonitrile in water (0.1% TFA) over 10 min at a flow rate of 0.8 mL/min. (Fig. 1)Results: Low-FAPI-contain method: The final specific activities(SA) were 83, 74, 51, 20, 13 GBq/μmole for FAPI-46 with 1.5, 2.0, 3.0, 7.0, 9.0ug, respectively. The chemical purity analyzed by HPLC 91.4%, 52.7%, 54.0%, 88.0%, and 91.1% for SA of 83, 74, 51, 20, and 13 GBq/μmole, respectively. The chemical purity by TLC citric buffer system were 96.5%, 75.3%, 80.0%, 93.9% and 95.1%. The pH value of final product were 3.0, 2.5-3.0, 2.5-3.0, 3.0, and 3.0 (Tab. 1) (Fig. 2,3).Standard 50ug-FAPI-contain method: The final SA was 19.9 GBq/μmole. The chemical purity was 98.6% by HPLC, and  98.9% by TLC. The pH value of final product was 4.5. (Tab. 2)(Fig. 4,5)Conclusions: The synthesis of [68Ga]Ga-FAPI-46 with different amounts of precursor was successfully tested. The low-FAPI-contain method showed large variation in labelling performance while standard 50ug-FAPI-contain method represents good labelling performance. This study suggests that the set of radiolabelling parameters of standard 50ug-FAPI-contain method is preferred to be applied to the fully automated synthesizer system and automatically transfer the products through a CM cartridge and sterile filter into the final product vial. This operation could be used in the future clinical practice of multi-dose application with good compliance with GMP related regulations in Taiwan.Acknowledgement: We acknowledged SOFIE for the provision of the precursor and technical support.