A Head-to-Head Comparison of Detection Rate and Tumor Uptake of FAPI, PSMA, and FDG PET/CT in Newly Diagnosed High-risk Prostate Cancer.

Abstract

PurposeThis study was designed to investigate the detection rate and tumor uptake of 18F-AlF-NOTA-De-FAPI PET/CT in newly diagnosed high-risk prostate cancer (PCa), compared with 68Ga-PSMA-11 and 18F-FDG PET/CT.Patients and methodsThis study enrolled 48 patients with biopsy-diagnosed, treatment-naive high-risk PCa who underwent 18F-AlF-NOTA-De-FAPI, 68Ga-PSMA-11, and 18F-FDG PET/CT between April and December 2024. A head-to-head comparison of detection rate and tumor uptake was performed among the 3 tracers. In addition, 18F-AlF-NOTA-De-FAPI and 68Ga-PSMA-11 dual-tracer PET was used to characterize the imaging phenotypes of each lesion and interlesional heterogeneity.ResultsA total of 477 lesions were detected by the 3 PET tracers. 68Ga-PSMA-11 exhibited the highest overall detection rate (96.4%), followed by 18F-AlF-NOTA-De-FAPI (81.1%) and 18F-FDG (66.0%). A total of 17 68Ga-PSMA-11-negative lesions were identified in 8 patients, all of which were detected by 18F-AlF-NOTA-De-FAPI, whereas only 12 were detected by 18F-FDG. Combined 68Ga-PSMA-11 and 18F-AlF-NOTA-De-FAPI PET identified all lesions detected by triple-tracer PET. Based on relative tracer dominance of dual-tracer PET, patients were classified as PSMA-dominant (n=23), FAPI-dominant (n=5), or mixed phenotype (n=20). The mixed phenotype with marked interlesional heterogeneity might be associated with more advanced clinical characteristics, with a higher proportion of metastatic disease and a greater metastatic burden.Conclusions18F-AlF-NOTA-De-FAPI is a promising PET tracer for newly diagnosed high-risk PCa. It may improve the detection rate of 68Ga-PSMA-11-negative lesions and provide complementary information that could reflect interlesional heterogeneity. The clinical value of combining 18F-AlF-NOTA-De-FAPI and 68Ga-PSMA-11 PET requires further validation in larger prospective cohorts.