Comparative Performance of ¹⁸F-FDG PET/CT and ⁶⁸Ga-FAPI PET/CT in TENIS Syndrome in Treated Differentiated Thyroid...

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.

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 (SUV_max) 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.

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 SUV_max (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.

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.