PET Imaging of Fibroblast Activation Protein in Various Cancers Using [ 18 F]AlF‑NOTA‑FAPI‑04: Comparison with 18 F-FDG in a Single-Center, Prospective Study.

RATIONALE AND OBJECTIVES: Targeting fibroblast-activation protein is a newer diagnostic approach for the visualization of tumor stroma, and a novel aluminum-[18 F] fluoride (Al18 F)-labeled fibroblast-activation protein inhibitor-4 (FAPI-04), hereafter [18 F] AlF-NOTA-FAPI-04, presents a promising alternative to gallium 68 (68 Ga)-labeled FAPI owing to its relatively longer half-life. This study sought to evaluate the clinical usefulness of [18 F] AlF-NOTA-FAPI-04 PET/CT for the diagnosis of various types of cancer, compared to [18 F] FDG PET/CT.

MATERIALS AND METHODS: In this prospective study conducted from October 2021 to January 2024, a total of 148 patients with 16 different tumor entities underwent contemporaneous 18 F-FDG and 18 F-FAPI-04 PET/CT either for an initial assessment or for recurrence detection. Uptake of 18 F-FDG and 18 F-FAPI-04 was quantified by the maximum standard uptake value (SUV max). Diagnostic sensitivity, specificity, and accuracy were compared by using the McNemar test between these two imaging agents.

RESULTS: 18 F-FAPI-04 PET/CT could clearly depict 16 different types of cancer with excellent image contrast, thereby leading to a higher detection rate of primary tumors than did 18 F-FDG PET/CT (98.06% vs. 81.55%, P＜0.001). In per-lymph node analysis, the sensitivity, specificity, and accuracy in the diagnosis of metastatic lymph nodes were 92.44%, 90.44%, and 91.56%, respectively, which was much higher than that 18 F-FDG PET/CT (80.23%, 79.41%, and 79.87%, respectively). Meanwhile, 18 F-FAPI-04 PET/CT outperformed 18 F-FDG PET/CT in identifying more suspected distant metastases (86.57% vs. 74.13%, P＜0.001). Furthermore, 18 F-FAPI-04 PET/CT upgraded tumor staging in 36/101 patients (35.6%), and detected tumor recurrence or metastases in 43/47 patients (91.49%).

CONCLUSION: Our findings demonstrated that primary and metastatic lesions in patients with various types of malignant tumors are well-visualized on 18 F-FAPI-04 PET/CT, which exhibited a superior diagnostic performance than 18 F-FDG PET/CT. Moreover, 18 F-FAPI-04 PET/CT is a promising tool for tumor staging and follow-up of various malignancies.