FAPI-04 PET/CT Using [(18)F]AlF Labeling Strategy: Automatic Synthesis, Quality Control, and In Vivo Assessment in Patient

(68)Ga labeled FAPI is the current standard for FAPI-PET, but its batch activity is limited. [(18)F]AlF-NOTA-FAPI-04 is a promising alternative combining the advantages of a chelator-based radiolabeling method with the unique properties of fluorine-18. The objective of this study was to develop a quick automatic method for synthesis of [(18)F]AlF-NOTA-FAPI-04 using a AllinOne synthesis system, and perform PET imaging with [(18)F]AlF-NOTA-FAPI-04 on patients. [(18)F]AlF-NOTA-FAPI-04 was produced, and its quality control was conducted by HPLC equipped with a radioactive detector. [(18)F]AlF-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice (n = 3) and 4T1 breast cancer models (n = 3) to determine its biodistribution. Then [(18)F]AlF-NOTA-FAPI-04 and (18)F-fluorodeoxyglucose (FDG) PET/CT imaging were performed in an invasive ductal carcinoma patient (female, 54 years old). The synthesis time of [(18)F]AlF-NOTA-FAPI-04 was about 25 min, and the radiochemical yield was 26.4 ± 1.5% (attenuation correction, n = 10). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0–7.5, and the specific activity was 49.41 ± 3.19 GBq/μmol. PET/CT imaging in mice showed that physiological uptake of [(18)F]AlF-NOTA-FAPI-04 was mainly in the biliary system and bladder, and [(18)F]AlF-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that [(18)F]AlF-NOTA-FAPI-04 obtained high tumor background ratio (TBR) value of 8.44 in segment V and VI, while TBR value was 2.55 by (18)F-FDG. [(18)F]AlF-NOTA-FAPI-04 could be synthesized with high radiochemical yield and batch production by AllinOne module and show excellent diagnosis performance in cancer patients.