Ga-68-FAPI for sarcoma imaging: Data from the FAPI-PET prospective observational trial

Introduction: Bone and soft tissue tumors are of mesenchymal origin and have been shown to express fibroblast activation protein (FAP) in tumor cells and cancer-associated fibroblast. Recently introduced radio-labelled FAP-Inhibitors (e.g. ⁶⁸Ga-FAPI46) have shown increased tumor uptake in positron emission tomography in sarcoma patients. Here we report the accuracy of FAPI-PET in a prospective trial.

Methods: Fortyseven patients with bone and soft tissue sarcoma undergoing clinical ⁶⁸Ga-FAPI-PET were enrolled into the FAPI-PET observational trial. Of these, 46 (92%) patients also underwent ¹⁸F-Fluordesoxyglucose-PET. Primary Endpoint was association of ⁶⁸Ga-FAPI-PET uptake intensity and histopathological FAP-expression. Secondary endpoints were detection rate, positive predictive value (PPV), detection rate, interrater reproducibility, and change in management.

Results: Primary endpoint was met and the association between FAPI-PET uptake intensity and histopathological FAP-expression was significant (p = 0.037). Lesions were validated by histopathology and if possible FAP-immunohistochemistry in 31 patients. Sensitivity and specificity for histopathologically confirmed lesions were 0.97 (95% CI, 0.82-1.0) and 0.50 (95% CI; 0.01-0.99). PPV was 0.97 (95% CI, 0.82-1.0) for any tumor and 0.74 (95% CI, 0.54-0.89) for histopathology-FAP-positive tumors on a per-patient basis. 327 lesions were detected by FAPI-PET/CT compared to 359 lesions by FDG-PET/CT. Clinical management changed in 19 (41.3%) patients after FAPI-PET/CT. In 7 (14%) patients FAPI-PET/CT resulted in an upstaging compared to FDG-PET/CT, in two patients (8%) it resulted in a downstaging. Readers showed substantial to almost perfect agreement for the defined regions (local Fleiss’ κ = 0.73;; distant nodalκ = 0.92; lung κ = 0.86; bone κ = 0.65 and other organs/tissues κ = 0.63) and fair agreement for local nodal staging κ = 0.33. Conclusion: We confirm an association of FAPI-PET uptake intensity and histopathological FAP expression in sarcoma patients. Additionally, we demonstrate high PPV and sensitivity for ⁶⁸Ga-FAPI-PET by blinded reads and histopathological validation.