Development and Pilot Clinical Study of a Novel FAP-Targeted PET Tracer for PET Imaging of Tumors

In recent years, fibroblast activation protein (FAP) has become a promising target, with FAPI tracers proving effective for tumor diagnosis. This study designs a novel FAPI tracer ([¹⁸F]AlF-AA-FAPT) for FAP imaging, aiming to enhance the pharmacokinetic properties of existing tracers, further enhancing tumor uptake, and reducing background uptake in nontarget organs. The radiochemical synthesis of [¹⁸F]AlF-AA-FAPT is simple, and the product has high purity, excellent in vitro and in vivo stability, hydrophilicity, and targeting affinity. Micro-PET/CT imaging demonstrates that [¹⁸F]AlF-AA-FAPT has higher tumor-specific uptake, lower tissue accumulation, and faster renal clearance than existing tracers [¹⁸F]AlF-FAPI-42 and [¹⁸F]AlF-FAPT. Our pilot clinical study directly compares [¹⁸F]AlF-AA-FAPT with [¹⁸F]FDG in six cancer patients, revealing that the novel tracer exhibits superior pharmacokinetic properties and provides enhanced imaging efficacy for both primary and metastatic lesions across certain cancer types. These results suggest that [¹⁸F]AlF-AA-FAPT demonstrates excellent target-to-background ratio and improves pharmacokinetic properties, making it an effective alternative to current FAPI tracers.