To automatically synthesize Al¹⁸F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors.

Al¹⁸F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al¹⁸F-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 Al¹⁸F-NOTA-FAPI-04 and ¹⁸F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old).

The synthesis time of Al¹⁸F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al¹⁸F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al¹⁸F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al¹⁸F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by ¹⁸F-FDG.

Al¹⁸F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al¹⁸F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.

Membrane proteins; Fibroblasts; Fluorine radioisotopes; Positron-emission tomography; Tomography, X-ray computed; Mice; Antagonists and inhibitors