Fibroblast Activation Protein identifies progressive bladder cancer and allows peritoneal metastasis detection by 68Ga-FAPI PET/CT imaging

Abstract Background: Currently, [18F] FDG-PET/CT scans are used in advanced bladder cancer patients to identify metastatic lesions. Unfortunately, FDG-PET/CT has a relatively low sensitivity for detecting metastatic disease in these patients, resulting in open-and-close operations due to unexpected metastatic disease. Recently a novel radiotracer has emerged using fibroblast activation protein (FAP) targeting [ 68 Ga] FAPI-46, sparking the question if this provides a more accurate alternative to [ 18 F] FDG-PET/CT for detecting metastatic lesions in bladder cancer patients. Methods: FAP expression was evaluated in primary and metastatic samples of two patients with muscle-invasive bladder cancer using immunohistochemical analysis. Finally, both FDG and FAPI scans were obtained and compared using [ 18 F] FDG-PET/CT and [ 68 Ga] FAPI-46-PET/CT. Results: FAP protein expression was found to be high in both primary and metastatic tumor lesions. In the primary tumor lesions, FAP expression was mainly see in the fibrotic area adjacent to the tumor bulk. In contrast, peritoneal metastases showed FAP expression closely surrounding small tumor clusters. Finally, metastatic lesions that were undetectable on [ 18 F] FDG-PET/CT were detected using [ 68 Ga] FAPI-46-PET/CT. FAPI-46-PET/CT findings of peritoneal metastases correlated with lesions found in the open-and-close surgical procedures. Conclusions: [ 68 Ga] FAPI-46-PET/CT provides a promising alternative to [ 18 F] FDG-PET/CT to identify peritoneal metastatic lesions of bladder cancer in high-risk patients.