68Ga-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.

Methods

PET/CT with 68Ga-FAPI-46 was performed in 18 patients (n = 9 with PSC, without proven CCC; n = 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 SUVpeak 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.

Results

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 SUVpeak did not differ between PSC and CCC (median, 8.8 [interquartile range, 6.3] vs. 15.0 [interquartile range, 9.2]; P = 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; r = 0.70, P = 0.04) and fibrosis-4 (r = 0.63, P = 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.

Conclusion

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.