Positron Emission Tomography with Fibroblast Activation Protein-Targeted Radiopharmaceuticals in Primary Hepatic Tumors: A Systematic Review

Background: This systematic review was performed to investigate the potential diagnostic role of fibroblast activation protein (FAP)-targeted radiopharmaceuticals in hepatocarcinoma (HCC) and cholangiocarcinoma (CCA). Methods: Relevant studies published between 2019 and 2023 were selected by searching PubMed and Scopus. The following data were extracted: authors, radiopharmaceuticals, sample size, country and year of publication, study design, and main results. Selected studies were analyzed using a modified version of the Critical Appraisal Skills Programme (CASP). Results: A total of 15 papers were finally selected, where 5 (33%) were retrospective, and 10 (67%) were prospective, with an overall number of 331 involved patients. Most of the studies (14/15, 93%) employed the FAP inhibitor series (FAPI), while only one research study used cyclic peptides as FAP-binding motifs. Twelve papers (80%) compared these FAP-targeted radiopharmaceuticals with 18F-FDG. The other 3/15 (20%) were not comparative studies and used exclusively 68Ga-FAPI-04. 68Ga-FAPI-04 is the most used radiopharmaceutical in analyzed studies (11/15, 73%), while other tracers, including 18F-FAPI, 68Ga-FAPI-46, and 68Ga-FAP-2286, were used in the remaining ones. Conclusions: FAP-targeted radiopharmaceuticals have good diagnostic accuracy in HCC and CCA, with potential and promising theragnostic applications.