A prospective, exploratory study of 18F-PSMA-1007 PET/CT in patients with medullary thyroid cancer

Prostate specific membrane antigen (PSMA) is expressed in the neo-vasculature of most medullary thyroid carcinomas (MTCs) and can be imaged with PET/CT. This prospective, feasibility study evaluated the diagnostic performance of 18F-PSMA-1007 PET/CT in MTC patients compared to 18F-FDG PET/CT. Eligible patients were ≥ 1 18 years, had histopathologically confirmed MTC, elevated calcitonin/CEA, and a clinically indicated 18F-FDG PET/CT. All imaging ≤ 1 year prior was reviewed to establish a composite reference standard (CRS) of total tumor lesions. Analyses were performed at patient, region (neck/thorax/abdomen/bone), and lesion level. Lesions were also semi-quantified using SUVpeak. In eight included patients, the CRS identified 186 tumor lesions. Patient-based sensitivity of 18F-PSMA-1007 PET/CT was 88% (median lesion per patient 3, range 2 – 51), while 100% for 18F-FDG PET/CT (lesions per patient 5, range 2 – 45). Of 32 evaluated regions, 16 (50%) were tumor positive, of which 18F-PSMA-1007 PET/CT and 18F-FDG PET/CT identified 12 (sensitivity 75%), and 14 (sensitivity 88%) correctly, respectively. 18F-PSMA-1007 PET/CT detected 84 lesions (sensitivity 45%) while the 18F-FDG PET/CT detected 85 (sensitivity 46%) of 186 tumor lesions (p = 0.893). Lesion-based semi-quantitative analysis identified a higher SUVpeak on 18F-PSMA-1007 (18F-PSMA-1007 3.37 (range 1.78 – 9.63) vs 18F-FDG PET/CT 2.52 (range 1.04 – 5.51) p < 0.001). In this exploratory, hypothesis-generating study, 18F-PSMA-1007 PET/CT shows modest utility in assessing disease extent in MTC patients. Its value in staging therefore seems limited when compared to existing imaging modalities. Nonetheless, high tracer uptake (exceeding the liver) in selected lesions might identify possible candidates for 177Lu-PSMA-617 therapy, warranting further research.