[18F]AlF-NOTA-FAPI-04 PET/CT improves detection of subcentimeter recurrent lesions in differentiated thyroid cancer

Abstract

Purpose: Fibroblast activation protein (FAP)-targeted PET/CT has emerged as a promising tool for visualizing tumor stroma. This study aimed to validate the diagnostic efficacy of [18F]AlF-NOTA-FAPI-04 PET/CT in detecting subclinical metastases in recurrent differentiated thyroid cancer (DTC), with direct comparison to [18F]FDG PET/CT. Methods: Twenty-three DTC participants with biochemical recurrence (suppressed thyroglobulin [Tg] ≥ 1 ng/mL or Tg antibodies [Tg-Ab] > 115 IU/mL) underwent [18F]AlF-NOTA-FAPI-04 PET/CT, including 16 who underwent paired [18F]FDG scans. Lesion classification followed histopathology or 15.5-month clinical follow-up (median, 8–32 months). Results: [18F]AlF-NOTA-FAPI-04 PET/CT demonstrated significantly higher lesion-level sensitivity (75% vs. 13%, P = 0.002) and accuracy (80% vs. 27%, P < 0.001) than [18F]FDG. Participant-level sensitivity reached 100% (7/7 vs. 14% [1/7], P = 0.003). Notably, 7 cervical lymph node metastases (mean diameter 5.9 ± 1.4 mm) were detected exclusively by FAPI imaging. Conclusion: [18F]AlF-NOTA-FAPI-04 PET/CT exhibits superior diagnostic performance over [18F]FDG PET/CT in detecting small metastatic lesions in recurrent DTC, potentially enabling earlier intervention and improved patient management.