Superior Tumor Detection for 68Ga-FAPI-46 Versus 18F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma

Management of cholangiocarcinoma is among other factors critically determined by accurate staging. Here, we aimed to assess the accuracy of PET/CT with the novel cancer fibroblast-directed 68Ga-fibroblast activation protein (FAP) inhibitor (FAPI)-46 tracer for cholan-giocarcinoma staging and management guidance.Methods: Patients with cholangiocarcinoma from a prospective observational trial were analyzed. 68Ga-FAPI-46 PET/CT detection efficacy was compared with 18F-FDG PET/CT and conventional CT. SUVmax/tumor-to-back-ground ratio (Wilcoxon test) and separately uptake for tumor grade and location (Mann-Whitney U test) were compared. Immunohisto-chemical FAP and glucose transporter 1 (GLUT1) expression of stromal and cancer cells was analyzed. The impact on therapy man-agement was investigated by pre-and post-PET/CT questionnaires sent to the treating physicians.Results: In total, 10 patients (6 with intrahepatic cholangiocarcinoma and 4 with extrahepatic cholangio-carcinoma; 6 with grade 2 tumor and 4 with grade 3 tumor) underwent 68Ga-FAPI-46 PET/CT and conventional CT; 9 patients underwent additional 18F-FDG PET/CT. Immunohistochemical analysis was per -formed on the entire central tumor plain in 6 patients. Completed questionnaires were returned in 8 cases. Detection rates for 68Ga-FAPI-46 PET/CT, 18F-FDG PET/CT, and CT were 5, 5, and 5, respec-tively, for primary tumor; 11, 10, and 3, respectively, for lymph nodes; and 6, 4, and 2, respectively, for distant metastases. 68Ga-FAPI-46 ver-sus 18F-FDG PET/CT SUVmax for primary tumor, lymph nodes, and dis -tant metastases was 14.5 versus 5.2 (P = 0.043), 4.7 versus 6.7 (P = 0.05), and 9.5 versus 5.3 (P = 0.046), respectively, and tumor-to -background ratio (liver) was 12.1 versus 1.9 (P = 0.043) for primary tumor. Grade 3 tumors demonstrated a significantly higher 68Ga-FAPI-46 uptake than grade 2 tumors (SUVmax, 12.6 vs. 6.4; P = 0.009). Immu-nohistochemical FAP expression was high on tumor stroma (-90% of cells positive), whereas GLUT1 expression was high on tumor cells (-80% of cells positive). Overall, average expression intensity was estimated as grade 3 for FAP and grade 2 for GLUT1. Positive 68Ga-FAPI-46 PET findings led to a consequent biopsy workup and diagnosis of cholangiocarcinoma in 1 patient. However, patient treatment was not adjusted on the basis of 68Ga-FAPI-46 PET.Conclusion: 68Ga-FAPI-46 demonstrated superior radiotracer up -take, especially in grade 3 tumors, and lesion detection in patients with cholangiocarcinoma. In line with this result, immunohistochem-istry demonstrated high FAP expression on tumor stroma. Accuracy is under investigation in an ongoing investigator-initiated trial.