## 4 Discussion  
Imaging plays a crucial role in the diagnosis of HCC and CCA. CT and MRI are the gold standard for non-invasive diagnosis and correct staging of the primary tumor. For HCC, MRI has greater sensitivity and specificity than CT [41], particularly for small lesions [42]. Similarly, MR colonagiography is used to identify CCA with a sensitivity of 100% and specificity of 95% [43, 44]. Currently, PET-CT imaging techniques are used in the oncology field for the diagnosis and staging of various tumors, being also useful in detecting distant metastases [45]. The most commonly used PET radiotracer is \({}^{18}\)F-FDG. Its mechanism is based on increased glucose metabolism in tumor cells, which have high levels of glucose transporter proteins (GLUT) and intracellular enzymes that promote glycolysis, leading to an accumulation of FDG in the tumor cell, especially if poorly differentiated [46]. For this reason, \({}^{18}\)F-FDG PET is also useful for distinguishing benign cases such as focal nodular hyperplasia (FNH), where FDG accumulation is similar to underlying physiological liver activity [47]. However, the role of \({}^{18}\)F-FDG PET in liver lesions is controversial, as it reports a sensitivity of 60.9% depending on the degree of differentiation and size of the tumor [48]. In fact, the liver is physiologically involved in glucose metabolism, leading to a notable uptake of FDG [49] with high background activity that does not allow a clear distinction in terms of TBR, particularly in well-differentiated HCCs, whose cells are similar to normal hepatocytes [46]. Therefore, \({}^{18}\)F-FDG PET is not appropriate for discriminating well-differentiated or small lesions. In ICC, the sensitivity of \({}^{18}\)F-FDG PET is 91-95%, dropping, however, to 60% in extrahepatic cholangiocarcinoma [50, 51]. Given the poor sensitivity of \({}^{18}\)F-FDG PET in some types of tumors, new targets have been identified, including TME and, specifically, the expression of FAP. FAP-targeted radiopharmaceuticals have therefore been developed to allow the detection of cancer types characterized by a strong desmoplastic reaction, such as breast, ovarian, lung, pancreatic, colorectal, and head-neck carcinomas [37, 52]. Also, in the immunohistochemical analysis of HCC and CCA, a significantly higher expression of FAP was observed compared to normal liver tissue [53], making FAP-targeted radiopharmaceuticals an attractive alternative to \({}^{18}\)F-FDG in terms of sensitivity. A recent study by [PERSON] et al. reported a sensitivity of 84.6% and 76.9% for the detection of malignant liver lesions with \({}^{18}\)F-FAPI-04 and \({}^{18}\)F-FDG, respectively [54]. The aim of this review is therefore to collect and describe published studies on the use of FAP-targeted radiopharmaceuticals in HCC and CCA. Overall, most studies have shown that \({}^{68}\)Ga-FAPI is more sensitive than \({}^{18}\)F-FDG for HCC and CCA with a sensitivity ranging from 85% to 100% rather than 51-87% of \({}^{18}\)F-FDG [29, 30, 31, 32, 33, 34, 36, 38], especially for small and well- and moderately differentiated lesions, as demonstrated by [PERSON] et al. finding a higher sensitivity than \({}^{18}\)F-FDG in detecting intrahepatic HCC lesions with a diameter \(\leq\) 2 cm (68.8% vs. 18.8%) and well- or moderately differentiated tumors (83.3% vs. 33.3%). In this study, the maximum standardized uptake value (SUVmax) was comparable between \({}^{68}\)Ga-FAPI-04 and \({}^{18}\)F-FDG, but the TBR was significantly higher in the \({}^{68}\)Ga-FAPI-04 group [31] (Figure 2). Even in terms of accuracy, the results seem promising [30, 36]. Only three studies reported the specificity values. According to their results, the specificity ranges from 72 to 100% [29, 30, 32]. Only two studies reported a worse specificity compared to \({}^{18}\)F-FGD, specifically 90% vs. 100% [30] and 72% vs. 76% [29].