Feasibility of [68Ga]FAPI-46 PET for assessing fibroinflammatory remodeling in experimental chronic colitis

Abstract

Fibroblast activation protein (FAP) is a hallmark of activated fibroblasts associated with tissue remodeling and fibrosis in chronic inflammatory bowel disease (IBD). However, current diagnostic tools remain invasive and unsuitable for longitudinal assessment of fibroinflammatory activity. This study evaluated the feasibility of [68Ga]FAPI-46 positron emission tomography (PET) for noninvasive imaging of fibroblast activation in a murine model of chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)–induced colitis. PET/CT was performed 40 min after [68Ga]FAPI-46 administration, followed by ex vivo analyses including histopathology, FAP immunohistochemistry, oxidative stress imaging, and western blotting of inflammatory mediators (TNF-α, IL-11). [68Ga]FAPI-46 PET showed relatively higher uptake in the inflamed colon of TNBS-treated mice than in controls (2.06 ± 0.14 vs. 1.70 ± 0.17 %ID/g, p = 0.01), corresponding to increased FAP expression and upregulation of inflammatory markers. Histology revealed mucosal injury with fibrotic remodeling, and oxidative stress imaging further supported ongoing fibroinflammatory activity. These findings provide preclinical evidence supporting the feasibility of [68Ga]FAPI-46 PET to visualize fibroblast activation and fibroinflammatory remodeling in chronic IBD. Although further validation in therapeutic and clinical studies is required, this approach may ultimately support longitudinal monitoring and quantitative evaluation of disease progression and treatment response. © 2026 Korean Chemical Society and Wiley-VCH GmbH.