PT  - JOURNAL ARTICLE
AU  - Pabst, Kim M.
AU  - Trajkovic-Arsic, Marija
AU  - Cheung, Phyllis F.Y.
AU  - Ballke, Simone
AU  - Steiger, Katja
AU  - Bartel, Timo
AU  - Schaarschmidt, Benedikt M.
AU  - Milosevic, Aleksandar
AU  - Seifert, Robert
AU  - Nader, Michael
AU  - Kessler, Lukas
AU  - Siveke, Jens T.
AU  - Lueckerath, Katharina
AU  - Kasper, Stefan
AU  - Herrmann, Ken
AU  - Hirmas, Nader
AU  - Schmidt, Hartmut H.
AU  - Hamacher, Rainer
AU  - Fendler, Wolfgang P.
TI  - Superior Tumor Detection for <sup>68</sup>Ga-FAPI-46 Versus <sup>18</sup>F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma
AID  - 10.2967/jnumed.122.265215
DP  - 2023 Apr 01
TA  - Journal of Nuclear Medicine
PG  - jnumed.122.265215
4099  - http://jnm.snmjournals.org/content/early/2023/04/06/jnumed.122.265215.short
4100  - http://jnm.snmjournals.org/content/early/2023/04/06/jnumed.122.265215.full
AB  - 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 68Gafibroblast activation protein (FAP) inhibitor (FAPI)-46 tracer for cholangiocarcinoma 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-background ratio (Wilcoxon test) and separately uptake for tumor grade and location (Mann–Whitney U 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. Results: 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 68Ga-FAPI-46 PET/CT and conventional CT; 9 patients underwent additional 18F-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 68Ga- FAPI-46 PET/CT, 18F-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. 68Ga-FAPI-46 versus 18F-FDG PET/CT SUVmax for primary tumor, lymph nodes, and distant 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). 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 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 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.