Potential application of [18F]AlF-PSMA-11 PET/CT in radioiodine refractory thyroid carcinoma

Background Patients diagnosed with radioiodine refractory (RAI-R) thyroid carcinoma (TC) have a significantly worse prognosis than patients with radiosensitive TC. These refractory malignancies are often dedifferentiated, hindering the effectiveness of iodine-based imaging. Additionally, the role of metabolic imaging using [F-18]FDG PET/CT is also limited in these cases, making adequate staging of RAI-R TC challenging. Recent case series have shown promising results regarding the role of the prostate-specific membrane antigen (PSMA) in TC. In this study we explored the value of [F-18]AlF-PSMA-11 PET/CT in RAI-R TC. Methods In this phase II study, lesions detected on [F-18]AlF-PSMA-11 PET were compared to findings from [18F]FDG PET/CT. Additionally, the serologic soluble prostate-specific membrane antigen (sPSMA) was measured using ELISA. PSMA-expression on tumor tissue in any available resection specimens was analysed with an immunostainer. Results Eight patients were included, with a total of 39 identified lesions based on PET imaging. [18F]AlF-PSMA-11 PET identified 30 of 39 lesions, and [F-18]FDG PET identified 33 lesions, leading to a detection rate of 76.9% and 84.6%, respectively. Interestingly, while nine lesions were solely visualized on [F-18]FDG, six were uniquely seen on [F-18]AlF-PSMA-11 PET. While sPSMA was immeasurable in all female patients, no correlation was found between sPSMA in male patients and disease-related factors. In five out of eight patients immunohistology showed PSMA expression on the primary tumor. Conclusions Although not all lesions could be visualized, [F-18]PSMA-11 PET identified multiple lesions imperceptible on [F-18]FDG PET. These results display the potential additional diagnostic role of PSMA-targeted imaging in patients with RAI-R TC.Trial registration number No. EudraCT 2021-000456-19.