[18F] Al -NOTA-FAPI-46 and [18F] FDG PET/CT in detecting postoperative residual and metastatic lesions of papillary thyroid cancer: a head-to-head comparative study

Background Postoperative staging and residual/metastatic lesion detection of papillary thyroid cancer (PTC) before radioiodine (RAI) ablation remains a critical clinical demand, especially for patients with intermediate to high-risk pathological features. Although 2-[ 18 F] fluoro-2-deoxy-D-glucose ([ 18 F] FDG) positron emission tomography/computed tomography (PET/CT) is widely applied in thyroid cancer imaging, its diagnostic sensitivity is suboptimal for small-volume, low-metabolic metastatic or residual lesions. Fibroblast activation protein (FAP), specifically overexpressed in tumor stromal cancer-associated fibroblasts (CAFs), has become a novel and reliable imaging target for oncological detection. This study aimed to head-to-head compare the diagnostic efficacy of [ 18 F]AL-NOTA-FAPI-46 ([ 18 F] FAPI-46) and [¹⁸F] FDG PET/CT in identifying postoperative residual and lymph node metastatic lesions in PTC patients prior to adjuvant ¹³¹I therapy. Methods A total of 18 consecutive postoperative PTC patients scheduled for ¹³¹I ablation were prospectively enrolled. All patients underwent paired [ 18 F] FAPI-46 and [ 18 F] FDG PET/CT within a 1-week interval before treatment. A composite reference standard integrating histopathological results, standardized imaging follow-up (median follow-up duration: 8 months, range: 6–12 months) and continuous clinical serological monitoring was adopted to verify lesion properties. Two experienced nuclear medicine physicians independently and blindly interpreted all PET/CT images in random order, with consensus arbitration for discrepant results. Quantitative imaging parameters including SUVmax and SUVpeak were calculated for all target lesions. Results For lymph node metastatic lesion detection, [ 18 F] FAPI-46 PET/CT exhibited significantly higher sensitivity (82.3% vs. 29.4%, exact two-tailed P = 0.022) and accuracy (78.3% vs. 30.4%) than [ 18 F] FDG PET/CT, with fewer false-positive cases (2 vs. 4). The true-positive lymph nodes showed significantly higher SUVmax (4.2 ± 3.2 vs. 1.6 ± 2.6, P = 0.015), SUVpeak (3.0 ± 2.1 vs. 1.0 ± 1.7, P = 0.005) on [ 18 F] FAPI-46 imaging than [ 18 F] FDG. Three false-positive bone lesions with increased [ 18 F] FAPI-46 uptake was found in two patients. These lesions were confirmed as benign fibroproliferative lesions via CT morphological features and follow-up imaging, and no true bone metastasis was detected in the entire cohort. Patients with confirmed lymph node metastasis had significantly higher serum stimulated thyroglobulin (sTg) levels (79.1 ± 51.1 ng/mL vs. 33.9 ± 36.5 ng/mL, P = 0.044). The optimal sTg diagnostic threshold for metastatic lesion screening was 25.9 ng/mL (AUC = 0.862), while the predictive value of this cutoff needs further large-sample validation. All enrolled patients had negative anti-thyroglobulin antibody (TgAb) status(< 15ng/mL) to eliminate serological detection interference. [ 18 F] FAPI-46 PET/CT successfully identified occult lymph node metastases in patients with elevated sTg and corrected the false-positive findings of [¹⁸F]FDG PET/CT. Conclusions In this prospective pilot study, [ 18 F] FAPI-46 PET/CT demonstrated superior diagnostic performance over [ 18 F] FDG PET/CT for detecting postoperative lymph node metastatic lesions in PTC patients before RAI ablation, with better capability to distinguish malignant lesions from reactive lymph nodes.