68Ga-FAPI-04 PET/CT has high diagnostic efficacy in Tg-positive and Tg-negative differentiated thyroid cancer.

BACKGROUND: Thyroglobulin (Tg) is a standard biomarker for monitoring differentiated thyroid carcinoma (DTC) after radioiodine therapy, yet its reliability is compromised by false-positive and false-negative results. This study aimed to evaluate the diagnostic performance of 68Ga-FAPI-04 PET/CT, an emerging imaging modality, for detecting recurrence and metastasis in DTC patients, regardless of their Tg status. METHODS: This retrospective study included patients with suspected or confirmed metastatic DTC who underwent 68Ga-FAPI-04 PET/CT between October 2022 and May 2025. All participants underwent 68Ga-FAPI-04 PET/CT and Tg testing, with histopathology or clinical follow-up as the reference standard. The sensitivity, specificity, and accuracy of both methods were compared. Quantitative analysis was performed using the target-to-background ratio (TBR). RESULTS: Among 99 patients in a TSH-suppressed state, 68Ga-FAPI-04 PET/CT demonstrated superior diagnostic accuracy (95.96%) compared to Tg testing (91.92%). In 48 TSH-stimulated patients, PET/CT maintained perfect accuracy (100%), outperforming Tg (97.92%). Notably, PET/CT successfully identified metastatic lesions in eight Tg-negative patients, primarily lymph node metastases. Using the mediastinum as a background for TBR calculation further enhanced the diagnostic efficacy for lymph node metastases, with the optimal threshold being 1.428, and achieving an accuracy and true positive rate of 0.98. CONCLUSION: 68Ga‑FAPI‑04 PET/CT exhibits high accuracy for diagnosing recurrence and metastasis in DTC, and importantly can identify lesions in Tg‑negative patients.