First Clinical Experience With 68GaGa-FAPI-46-PET/CT Versus 18FF-FDG PET/CT for Nodal Staging in Cervical Cancer

INTRODUCTION: In several solid tumors, fibroblast activation protein (FAP) is overexpressed by cancer-associated fibroblasts in the tumor microenvironment. Preliminary evidence suggests that detection and staging are feasible with PET/CT imaging using 68Ga-radiolabeled inhibitors of FAP also in cervical cancer (CC). Our study aims to explore the accuracy of 68GaGa-fibroblast activation protein inhibitor (FAPI)-46 PET/CT and 18FF-FDG PET/CT compared with histopathological results of surgical lymph node (LN) staging before primary chemoradiation. METHODS: Seven consecutive women with treatment-naive and biopsy-proven locally advanced CC underwent both whole-body 68GaGa-FAPI-46- and 18FF-FDG PET/CT, for imaging nodal staging before systematic laparoscopic lymphadenectomy of the pelvic and para-aortic region. Location and number of suspicious LNs in PET imaging were recorded and compared with the results of histopathological analysis, including immunohistochemical staining for FAP. RESULTS: All 7 patients had focal uptake above background in their tumor lesions in 68GaGa-FAPI-46 PET/CT. 68GaGa-FAPI-46 PET/CT showed a higher tumor-to-background ratio (TBR) in primary tumor as well as in LN metastasis. Median TBRmax values using liver were 32.02 and 5.15 for 68GaGa-FAPI-46 PET/CT and 18FF-FDG PET/CT, respectively. Median TBRmax using blood pool was 18.45 versus 6.85 for 68GaGa-FAPI-46 PET/CT and 18FF-FDG PET/CT, respectively. Higher TBR also applies for nodal metastasis: TBRmax was 14.55 versus 1.39 (liver) and 7.97 versus 1.8 (blood pool) for 68GaGa-FAPI-46 PET/CT and 18FF-FDG PET/CT, respectively. Overall, 68GaGa-FAPI-46 PET/CT detected more lesions compared with 18FF-FDG PET/CT. Following surgical staging, a total of 5 metastatic LNs could be pathologically confirmed, of which 2 and 4 were positive by 18FF-FDG PET/CT and 68GaGa-FAPI-46 PET/CT, respectively. CONCLUSION: 68GaGa-FAPI-46 PET/CT seems useful to improve detection of nodal metastasis in patients with CCs. Future studies should aim to compare 68GaGa-FAPI-46 PET/CT to surgical staging of pelvic and para-aortic LNs in patients with locally advanced CC.