Comparative analysis of [18F]F-FAPI PET/CT, [18F]F-FDG PET/CT and magnetization transfer MR imaging to detect intestinal fibrosis in Crohn’s disease: A prospective animal model and human cohort study

Purpose Accurately and early detection of intestinal fibrosis in Crohn’s disease (CD) is crucial for clinical management yet remains an unmet need. Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as a promising tool to assess fibrosis. We aimed to investigate the diagnostic capability of [ 18 F]F-FAPI PET/CT in detecting intestinal fibrosis and compared it with[ 18 F]F-FDG PET/CT and magnetization transfer MR imaging (MTI). Methods Twenty-two rats underwent TNBS treatment to simulate fibrosis development, followed by three quantitative imaging sessions within one week. Mean and maximum standardized uptake values (SUV mean and SUV max ) were calculated on[ 18 F]F-FAPI and [ 18 F]F-FDG PET/CT, along with normalized magnetization transfer ratio on MTI. Intestinal fibrosis was assessed pathologically, with MTI serving as imaging standard for fibrosis. The diagnostic efficacy of imaging parameters in fibrosis was compared using pathological and imaging standards. Ten patients with 34 bowel strictures were prospectively recruited to validate their diagnostic performance, using the identical imaging protocol. Results In CD patients, the accuracy of FAPI uptake (both AUCs = 0.87, both P ≤ 0.01) in distinguishing non-to-mild from moderate-to-severe fibrosis was higher than FDG uptake (both AUCs = 0.82, P ≤ 0.01) and comparable to MTI (AUCs = 0.90, P ≤ 0.001). In rats, FAPI uptake responded earlier to fibrosis development than FDG and MTI; consistently, during early phase, FAPI uptake showed a stronger correlation (SUV mean : R = 0.69) with pathological fibrosis than FDG (SUV mean : R = 0.17) and MTI ( R = 0.52). Conclusion The diagnostic efficacy of [ 18 F]F-FAPI PET/CT in detecting CD fibrosis is superior to [ 18 F]F-FDG PET/CT and comparable to MTI, exhibiting great potential for early detection of intestinal fibrosis.