Head-to-head comparison of [18F] fluorodeoxyglucose PET/CT and [68Ga]Ga-prostate specific membrane antigen-11 PET/CT in radioactive iodine refractory differentiated thyroid cancer

Objectives Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is associated with challenges in both imaging and treatment due to resistance to I-131. The aim of this study is to compare the lesion detection rates of [ 18 F] fluorodeoxyglucose (FDG) PET/computed tomography [CT] and [ 68 Ga]Ga-prostate specific membrane antigen (PSMA)-11 PET/CT, and to investigate the theranostic potential of PSMA in RAIR-DTC. Methods Thirty-eight RAIR-DTC patients followed between 2022 and 2024 underwent [ 18 F]FDG PET/CT and [ 68 Ga]Ga-PSMA-11 PET/CT. Lesions with uptake exceeding background activity were considered positive, while physiological uptake areas and benign-appearing foci were excluded. Lesion maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), and detection rates were calculated and compared. Results [ 18 F]FDG PET/CT detected more lesions overall than [ 68 Ga]Ga-PSMA-11 PET/CT (96.8 vs. 60.1%), particularly in the thyroid bed, lymph nodes, and lungs. However, both modalities identified the same number of bone lesions. While [ 18 F]FDG PET/CT was superior in most patients, [ 68 Ga]Ga-PSMA-11 PET/CT detected more lesions in a subset of patients and performed better in the pure classic papillary thyroid carcinoma subtype compared to other subtypes (71.7 vs. 50.3%). SUVmax and TBR values were higher on [ 18 F]FDG PET/CT, yet in 14 patients (36.8%), [ 68 Ga]Ga-PSMA-11 PET/CT identified lesions with SUVmax exceeding liver SUVmax, indicating potential eligibility for PSMA-based radionuclide therapy. Conclusion Although [ 18 F]FDG PET/CT demonstrated superior overall lesion detection, [ 68 Ga]Ga-PSMA-11 PET/CT identified more lesions in a subset of patients. [ 68 Ga]Ga-PSMA-11 PET/CT appears to be more beneficial in the pure classic subtype compared to other histological variants. Notably, [ 68 Ga]Ga-PSMA-11 PET/CT demonstrated high uptake in a considerable number of patients and may provide theranostic value in RAIR-DTC patients with limited treatment options.