Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and has a good prognosis when appropriately treated. However, approximately 5%‒15% of DTC develop radioiodine refractoriness (RAIR), limiting therapeutic options and significantly impacting patient survival. Studies have shown prostate-specific membrane antigen (PSMA) uptake in advanced DTC, making this antigen a potential diagnostic and therapeutic target.

To compare the uptake between 18F-PSMA and 18F-FDG radiotracers on PET-CT scans in RAIR-DTC patients. In selected patients with no viable therapeutic alternatives, to evaluate the use of 177Lu-PSMA radiopharmaceutical as a compassionate treatment option.

Patients diagnosed with RAIR-DTC were selected. All patients underwent both 18F-FDG and 18F-PSMA PET-CT scans. The regions of radiotracer uptake, the maximum SUV (SUVmax) of each region, and the highest SUVmax among all regions were evaluated for each exam. Subsequently, a subgroup of patients demonstrating intense uptake on the 18F-PSMA PET-CT scan was selected. Each of these patients was treated with 177Lu-PSMA at a total dose of 600 mCi, divided into three monthly administrations. These patients were monitored with periodic laboratory and imaging tests to assess potential adverse reactions and response to Lutetium therapy.

A total of 34 patients were recruited, with a mean age of 59.8 years, a female predominance (73.5%), and a mean follow-up time of 9.6 years. All patients showed uptake of both radiotracers, with slight variations in intensity and regions. Three patients completed the 177Lu-PSMA treatment without significant side effects. During the first 12 months of follow-up, Thyroglobulin levels remained stable in patient 1, and increased by 28% and 41% in patients 2 and 3, respectively. Regarding tumor dimensions, Patients 1 and 2 remained stable, while an increase of 1.4 cm in a cervical lesion was observed in patient 3. Concerning the development or disappearance of lesions, Patient 1 presented a new bone lesion visualized only on 18F-FDG starting at the 6th month, while in patient 2, a pre-existing liver lesion ceased to show uptake on 18F-PSMA from the 3rd month onwards.

18F-PSMA PET-CT showed uptake in all selected patients, and both the number of regions and the maximum SUV were similar to 18F-FDG, data which support its non-inferiority. The compassionate therapeutic administration of 177Lu-PSMA proved to be safe and well-tolerated; however, due to the more insidious nature characteristic of DTC, data regarding its efficacy are still pending further follow-up of these patients.