AL[18F]-NOTA-FAPI-46 and [18F]FDG PET/CT in Detecting Postoperative Recurrence and Metastasis of Papillary Thyroid Cancer: A Head-to-Head Comparative study

Background Postoperative monitoring of papillary thyroid cancer (PTC), especially in cases of biochemical recurrence or radioiodine-refractory disease, remains challenging. Although 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) is widely used, its sensitivity is suboptimal, particularly for lesions with low metabolic activity or small metastases. Fibroblast activation protein (FAP), expressed in the tumor stroma, has emerged as a promising target. This study aimed to compare the diagnostic efficacy of Al [¹⁸F]-NOTA-FAPI-46([¹⁸F]FAPI-46) and [¹⁸F]FDG PET/CT in detecting recurrence and metastasis in postoperative PTC patients. Results [¹⁸F]FAPI-46 PET/CT demonstrated significantly higher sensitivity (82.3% vs. 29.4%, P = 0.022) and accuracy (78.3% vs. 30.4%) than [¹⁸F]FDG PET/CT for detecting lymph node metastases, with fewer false-positive cases (2 vs. 4). However, [¹⁸F]FAPI-46 showed three false-positive bone lesions (SUVₘₐₓ: 7.7–7.9), likely due to benign fibroproliferative changes. In patients with metastasis, serum stimulated thyroglobulin (sTg) levels were significantly elevated (79.1 ± 51.1 ng/mL vs. 33.9 ± 36.5 ng/mL, P = 0.044), with an optimal diagnostic threshold of 25.9 ng/mL (AUC = 0.862). [¹⁸F]FAPI-46 PET/CT identified occult metastases in cases with elevated sTg and clarified false-positive [¹⁸F]FDG findings. Conclusions [¹⁸F]FAPI-46 PET/CT shows superior performance over [¹⁸F]FDG PET/CT in diagnosing lymph node metastases in postoperative PTC patients and effectively distinguishes metastatic from reactive lymph nodes. Caution is warranted for false-positive bone lesions, emphasizing the need for correlation with CT morphology.