Superior Tumor Detection for Ga-FAPI-46 Versus F-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 Ga-fibroblast activation protein (FAP) inhibitor (FAPI)-46 tracer for cholangiocarcinoma staging and management guidance. Patients with cholangiocarcinoma from a prospective observational trial were analyzed. Ga-FAPI-46 PET/CT detection efficacy was compared with F-FDG PET/CT and conventional CT. SUV/tumor-to-background ratio (Wilcoxon test) and separately uptake for tumor grade and location (Mann-Whitney test) were compared. Immunohistochemical FAP and glucose transporter 1 (GLUT1) expression of stromal and cancer cells was analyzed. The impact on therapy management was investigated by pre- and post-PET/CT questionnaires sent to the treating physicians. In total, 10 patients (6 with intrahepatic cholangiocarcinoma and 4 with extrahepatic cholangiocarcinoma; 6 with grade 2 tumor and 4 with grade 3 tumor) underwent Ga-FAPI-46 PET/CT and conventional CT; 9 patients underwent additional F-FDG PET/CT. Immunohistochemical analysis was performed on the entire central tumor plain in 6 patients. Completed questionnaires were returned in 8 cases. Detection rates for Ga-FAPI-46 PET/CT, F-FDG PET/CT, and CT were 5, 5, and 5, respectively, for primary tumor; 11, 10, and 3, respectively, for lymph nodes; and 6, 4, and 2, respectively, for distant metastases. Ga-FAPI-46 versus F-FDG PET/CT SUV for primary tumor, lymph nodes, and distant metastases was 14.5 versus 5.2 ( = 0.043), 4.7 versus 6.7 ( = 0.05), and 9.5 versus 5.3 ( = 0.046), respectively, and tumor-to-background ratio (liver) was 12.1 versus 1.9 ( = 0.043) for primary tumor. Grade 3 tumors demonstrated a significantly higher Ga-FAPI-46 uptake than grade 2 tumors (SUV, 12.6 vs. 6.4;  = 0.009). Immunohistochemical 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 Ga-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 Ga-FAPI-46 PET. Ga-FAPI-46 demonstrated superior radiotracer uptake, especially in grade 3 tumors, and lesion detection in patients with cholangiocarcinoma. In line with this result, immunohistochemistry demonstrated high FAP expression on tumor stroma. Accuracy is under investigation in an ongoing investigator-initiated trial.