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

Abstract

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. 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). 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. 68Ga‑FAPI‑04 PET/CT exhibits high accuracy for diagnosing recurrence and metastasis in DTC, and importantly can identify lesions in Tg‑negative patients.