Observation on Discordant Treatment Response on [ ¹⁸ F]FDG and [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT in Radioiodine-Refractory...

Dual-tracer positron emission tomography/computed tomography (PET/CT) using [ ¹⁸ F]FDG and fibroblast activation protein inhibitor (FAPI) provides complementary metabolic and stromal information in radioiodine-refractory differentiated thyroid carcinoma (DTC). However, response patterns during systemic therapy remain incompletely understood.

A 60-year-old male with papillary thyroid carcinoma (pT2 pN1a pM0) underwent total thyroidectomy and bilateral neck dissection. After defaulting from follow-up, he developed diffuse pulmonary and mediastinal metastases. Following one therapeutic dose of 200 mCi (7.4 GBq) [ ¹³¹ I], the disease became radioiodine-refractory (thyroglobulin-elevated negative iodine scintigraphy syndrome). Baseline Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography ([ ¹⁸ F]FDG PET/CT) demonstrated hypermetabolic pulmonary and mediastinal metastases. Gallium-68 fibroblast activation protein inhibitor Positron Emission Tomography/Computed Tomography ([ ⁶⁸ Ga]Ga-FAPI-04 PET/CT) performed the following day showed corresponding fibroblast activation protein expression without discordant lesions, although there was a low expression profile of [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT observed at the baseline compared with the [ ¹⁸ F]FDG PET/CT. After 10 months of lenvatinib (14 mg once daily), [ ¹⁸ F]FDG PET/CT demonstrated stable metabolic disease according to PERCIST 1.0 criteria, whereas [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT showed marked reduction of FAP expression in mediastinal nodes and several pulmonary nodules. Serum thyroglobulin decreased from 574 ng/mL to 457 ng/mL without anti-thyroglobulin antibody interference. The multidisciplinary team classified the case as stable disease based on persistent FDG avidity.

Discordant response patterns between FDG and FAPI PET/CT highlight the complementary biological information provided by dual-tracer imaging. Reduction in stromal FAP expression did not equate to metabolic remission. Combined interpretation may improve response assessment in radioiodine-refractory DTC.