Head-to-head comparison of 18F-PSMA and 18F-FDG PET/CT in locoregionally advanced head and neck squamous cell carcinoma: a pilot study.

OBJECTIVE

To compare the diagnostic performance of 18F-fluorodeoxyglucose (18F-FDG) and 18F-PSMA-1007 PET/CT in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC).

METHODS

Fourteen patients with HNSCC meeting locoregionally advanced criteria at PET/CT (stage III-IVB at presentation and/or locoregionally advanced recurrence/progression) underwent 18F-FDG and 18F-PSMA-1007 PET/CT from September 2023 to December 2024; imaging was performed at diagnosis or locoregional recurrence, and one had a stage II primary imaged during locoregionally advanced recurrence. Detection rates of primary and metastatic lesions and standardized uptake values (SUVmax) were assessed and compared between tracers.

RESULTS

18F-FDG PET/CT identified all primary lesions and metastatic lesions, whereas 18F-PSMA-1007 showed uptake in 10/13 evaluable primary tumors (76.9%) and in 6/13 patients with metastatic disease (46.2%). The median SUVmax values of primary tumors at 1 h and 2 h post-injection were significantly higher with 18F-FDG PET/CT compared to 18F-PSMA-1007 PET/CT (21.0 [IQR = 19.1] vs. 4.3 [IQR = 2.7] and 24.2 [IQR = 17.4] vs. 5.8 [IQR = 2.3], respectively; p < 0.001). In larger tumors, both tracers exhibited distinct intralesional uptake patterns, suggesting different biological targets.

CONCLUSION

18F-FDG PET/CT demonstrated superior lesion detection compared to 18F-PSMA-1007 PET/CT in advanced HNSCC. However, the complementary distribution of both tracers indicates that glycolytic activity and neovascular PSMA expression may coexist in tumors. These findings highlight the potential role of 18F-PSMA-1007 PET/CT as an adjunct to 18F-FDG PET/CT for the biological characterization of HNSCC, particularly in identifying angiogenic regions that may not be captured by conventional metabolic imaging.