Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and generally has a good prognosis when properly treated. However, approximately 5-15% of cases become refractory to radioiodine therapy (rRIT), limiting diagnostic and therapeutic options and significantly impacting patient survival. Recent studies have demonstrated prostate-specific membrane antigen (PSMA) uptake in positron emission tomography/computed tomography (PET/CT) scans of advanced DTC, suggesting its potential as a diagnostic imaging target and possibly opening new avenues for theranostic approaches.

To compare 18F-PSMA and 18F-fluorodeoxyglucose (18F-FDG) PET/CT scans of patients with rRIT DTC.

This cross-sectional study included 21 patients with rRIT DTC and locoregional or distant metastases. All patients underwent both 18F-FDG PET/CT and 18F-PSMA PET/CT scans. Uptake intensity was assessed using the maximum standardized uptake value (SUVmax), and lesion location was categorized as thyroid bed, cervical, thoracic, and abdominal lymph nodes, lungs, liver, and bones. The median SUVmax (range) was calculated for both radiotracers.

Both radiotracers detected lesions in all patients. The number of patients with active disease identified by 18F-FDG PET/CT and 18F-PSMA PET/CT, respectively, in each region was: thyroid bed (6 vs. 5), cervical lymph nodes (15 vs. 15), thoracic lymph nodes (11 vs. 11), abdominal lymph nodes (3 vs. 0), lungs (16 vs. 15), bones (4 vs. 6), and liver (1 vs. 1). In five patients, 18F-FDG identified more affected regions than 18F-PSMA, while in three patients, the opposite was observed. The median SUVmax was 24.2 (5.6–80.9) for 18F-FDG and 17.3 (4.1–73.3) for 18F-PSMA. In 12 patients (57.14%), the SUVmax of 18F-PSMA was higher than that of 18F-FDG.

Both radiotracers demonstrated uptake in at least some lesions in all rRIT DTC patients. Uptake intensity varied among lesions, with some showing higher 18F-FDG uptake and others higher 18F-PSMA uptake, suggesting a potential complementary role for these tracers in this disease. 18F-PSMA demonstrated a higher SUVmax than 18F-FDG in more than half of the patients, indicating that, in selected cases, PSMA-labeled theranostic approaches may be a viable option.