⁶⁸ Ga-FAPI-46 PET/CT in Primary Sclerosing Cholangitis and Suspected Cholangiocarcinoma

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease marked by fibrosis, strictures, and a high risk for developing cholangiocarcinoma (CCC). Recognition of CCC in PSC remains a diagnostic challenge. PET/CT using fibroblast activation protein inhibitors (FAPI) has emerged as a promising imaging modality in CCC, but its potential in the specific profibrotic setting of PSC has not yet been explored to the best of our knowledge. <b>Methods:</b> PET/CT with ⁶⁸Ga-FAPI-46 was performed in 18 patients (<i>n</i> = 9 with PSC, without proven CCC; <i>n</i> = 7 without PSC, with histologically confirmed CCC; 2 with both PSC and CCC). Results were correlated with endoscopic retrograde cholangiopancreatography, laboratory parameters, and fibrosis-4 as well as albumin-bilirubin scores. Five subjects who underwent FAPI PET/CT without hepatic disease or cancer diagnosis served as controls. For PET analysis, physiologic FAPI uptake was defined as mean SUV_peak of all controls plus 2 SD. Nonphysiologic liver uptake patterns were visually classified, and a fibroblast activation protein (FAP) liver volume above physiologic uptake (FAP-livo) was calculated. <b>Results:</b> The physiologic liver FAP signal was low and homogeneous in controls (SUV, 1.5 + 0.2). In CCC and PSC, the liver FAP signal was elevated with a FAP-livo of 1,362 ± 1,302 mL (CCC) and 1,286 ± 835 mL (PSC). Lesion SUV_peak did not differ between PSC and CCC (median, 8.8 [interquartile range, 6.3] vs. 15.0 [interquartile range, 9.2]; <i>P</i> = 0.72). Lesions were reliably detected in all patients with CCC and combined PSC/CCC. In PSC, 2 distinct patterns of the FAP signal existed, either along bile ducts or with field-shaped enhancement. FAP-livo was generally associated with decreased liver function (albumin-bilirubin score; <i>r</i> = 0.70, <i>P</i> = 0.04) and fibrosis-4 (<i>r</i> = 0.63, <i>P</i> = 0.08), and clinical parameters showed specific differences in the 2 distinct imaging pattern subsets of PSC. Because of the nononcological FAP signal elevation in active PSC regions, additional detection of focal lesions typical for CCC was not feasible. <b>Conclusion:</b> Active PSC is associated with elevated FAP expression, up to the level of CCC. Although this complicates the detection of PSC-associated CCC, FAPI PET/CT may be used for the assessment of PSC activity. This provides a rationale for future studies using FAPI PET/CT as a measure of fibrotic disease progression risk or response to antiinflammatory and antifibrotic therapy in PSC.