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

Abstract 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. 68Ga-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 68Ga-PSMA PET/CT and evaluate the response to 177Lu-PSMA-617 therapy in patients with RAI-refractory DTC. Materials and methods Five patients with RAI-refractory DTC underwent 68Ga-PSMA PET/CT to determine their eligibility for 177Lu-PSMA-617 therapy. 68Ga-PSMA PET/CTs were analyzed visually and quantitatively. Response to 177Lu-PSMA-617 therapy was evaluated using imaging and thyroglobulin (Tg) values. Results Tracer uptake suspicious for distant metastases was depicted in all 68Ga-PSMA PET/CTs. Based on tracer uptake, three patients were eligible for 177Lu-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 68Ga-PSMA PET/CT could be compared to 18FDG PET/CT in three patients. Two patients showed additional lesions on 68Ga-PSMA PET/CT, and one patient showed concordant imaging. Conclusion 68Ga-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 18FDG PET/CT. Furthermore, 68Ga-PSMA PET/CT might be used to identify patients eligible for treatment with 177Lu-PSMA-617. One of the two patients who underwent 177Lu-PSMA-617 therapy showed a modest, temporary response. To draw conclusions about the effectiveness of this therapy, more research is needed.