Comparative Performance of 18F-FDG PET/CT and 68Ga-FAPI PET/CT in TENIS Syndrome in Treated Differentiated Thyroid Carcinoma.
Objectives Thyroglobulin-elevated negative iodine scintigraphy (TENIS) syndrome presents a significant diagnostic challenge in the management of differentiated thyroid carcinoma (DTC). Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is the established imaging modality for detecting presence of structural disease, Gallium-68 (68Ga)-fibroblast activation protein inhibitor (FAPI) PET/CT, which targets the tumor stroma, represents a promising new alternative. This study directly compared the lesion detection capabilities of both tracers in patients with TENIS. Methods In this prospective single-center study (2021-2024), 22 patients with TENIS syndrome underwent both 18F-FDG and 68Ga-FAPI PET/CT scans within a 7-day interval of each other. Lesion detectability and maximum standardized uptake values (SUVmax) were compared between the two modalities. Lesions were validated using histopathology or cytopathology, biochemical response to empirical 131I therapy, imaging correlation or progression, and clinical progression methods. Results Among 22 patients (median age 43.5 years, 90% with papillary carcinoma), 18F-FDG was positive in 23/33 cervical lymph nodes, whereas 68Ga-FAPI was positive in 14/33 lymph nodes. Fourteen lymphnodes were positive on both modalities with comparable SUVmax (median 18F-FDG 3.3 vs. 68Ga-FAPI 3.6, p=0.689). All local recurrences in thyroid bed (n=4) were 18F-FDG-positive, whereas only 3 of the local recurrences were 68Ga-FAPI-positive. Distant metastases (lung and bone) showed similar detection rates. Conclusion 18F-FDG PET/CT demonstrates superior lesion detectability, particularly for cervical lymph nodes, in TENIS syndrome. 68Ga-FAPI PET/CT provides complementary information with comparable semiquantitative uptake in detected lesions but with lower overall detection. 18F-FDG PET/CT remains the preferred imaging modality for comprehensive disease evaluation in patients with radioactive iodine-refractory DTC.