(68)Ga-PSMA PET/CT in radioactive iodine-refractory differentiated thyroid cancer and first treatment results with (177)Lu-PSMA-617

BACKGROUND: Differentiated thyroid carcinoma (DTC) is the most common type of thyroid cancer. Treatment with surgery, radioactive iodine (RAI), and TSH suppression is effective in most patients. Five to 15% of patients become RAI refractory and need alternative therapy; however, treatment options are limited. (68)Ga-PSMA PET/CT, originally developed for prostate cancer, is also applicable to other malignancies, including thyroid carcinoma. The uptake of PSMA in thyroid carcinoma gives opportunities for imaging and therapy of RAI-refractory DTC. The aim of this study was to analyze imaging on (68)Ga-PSMA PET/CT and evaluate the response to (177)Lu-PSMA-617 therapy in patients with RAI-refractory DTC. MATERIALS AND METHODS: Five patients with RAI-refractory DTC underwent (68)Ga-PSMA PET/CT to determine their eligibility for (177)Lu-PSMA-617 therapy. (68)Ga-PSMA PET/CTs were analyzed visually and quantitatively. Response to (177)Lu-PSMA-617 therapy was evaluated using imaging and thyroglobulin (Tg) values. RESULTS: Tracer uptake suspicious for distant metastases was depicted in all (68)Ga-PSMA PET/CTs. Based on tracer uptake, three patients were eligible for (177)Lu-PSMA-617 therapy, of whom two were treated. One patient showed disease progression on imaging 1 month later, while her Tg values gradually increased from 18 to 63 μg/L in the months after treatment. Another patient showed partial, temporary response of lung and liver metastases. Her Tg levels initially decreased from 17 to 9 μg/L. However, 7 months after treatment, there was disease progression on imaging and Tg levels had increased to 14 μg/L. Imaging with (68)Ga-PSMA PET/CT could be compared to (18)FDG PET/CT in three patients. Two patients showed additional lesions on (68)Ga-PSMA PET/CT, and one patient showed concordant imaging. CONCLUSION: (68)Ga-PSMA PET/CT appears to have added value in patients with RAI-refractory DTC, as it is able to detect various types of lesions, some of which were not picked up by (18)FDG PET/CT. Furthermore, (68)Ga-PSMA PET/CT might be used to identify patients eligible for treatment with (177)Lu-PSMA-617. One of the two patients who underwent (177)Lu-PSMA-617 therapy showed a modest, temporary response. To draw conclusions about the effectiveness of this therapy, more research is needed.