Assessing the performance of Ga-68-Fibroblast activating protein inhibitor-04 (FAPI) in the diagnosis the cholangiocarcinoma

Introduction: Cholangiocarcinoma (CC) is mainly diagnosed and managed based on the clinical presentation & imaging criteria. Unlike other malignancies, positive pre-op cytology or histology is not routinely sought due to high proportion of fibrosis in CC results in less positivity rates in the tissue samples. There is a need for accurate non-invasive modalities to diagnose and stage these malignancies. Our aim was to study the utility of Ga-68 FAPI PET/CT in diagnosing the CC and to compare its performance with F18 FDG PET/CT.

Methods: Patients suspected to have CC were recruited prospectively. FDG and FAPI PET/CT studies were completed within 1 week. Final diagnosis of malignancy was achieved by tissue diagnosis (Either histopathological examination or fine needle aspiration cytology) and radiological correlation from conventional modalities. Results were compared with final diagnosis and expressed as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA).

Results: A total of 21 patients were included. 10 were intra-hepatic cholangiocarcinoma (IHCC) and 11 were extra-hepatic cholangiocarcinoma (EHCC). Median FDG SUVmax, FAPI SUVmax of primary tumour were 7.26 (4.46-16.30) and 17.7 (6.5420.53) respectively. Median metabolic tumour volume (MTV) and Fibrotic tumour volume (FTV) were 9.14 (3.69-318) and 21.3 (3.65-450) respectively. Median tumor to background ratio (TBR) with FDG, FAPI were 3.01 (1.86-5.66) and 7.15 (1.53-21.14) respectively. Difference in SUVmax and TBR between FDG PET/CT & FAPI-PET/CT was statistically significant. For overall diagnosis of CC, FAPI PET/CT clearly superseded FDG PET/CT with sensitivity, specificity & accuracy of 94.4%, 100% & 95.24% respectively, whereas for FDG PET/CT sensitivity, specificity & accuracy were 50%, 100% & 57.14% respectively. For the evaluation of IHCC & EHCC, FAPI PET/CT showed accuracy of 90%, whereas FDG PET/CT showed accuracy of 70% & 63% respectively. Only 3 patients showed metastatic disease, all lesions were noted in both the modalities.

Conclusions: FAPI PET/CT showed a clear superiority over FDG PET/CT in diagnosing the primary and metastatic cholangiocarcinoma. Presence of diffuse FAPI uptake in liver and biliary tract does not hamper the lesion detection in majority of cases.