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Introduction: The development of an intestinal stricture in patients with Crohn's disease represents an important and frequent complication, reflecting the progressive nature of the disease. Depending on the inflammatory and fibrotic composition of the stricture, intensified medical therapy, interventional endoscopy, or surgical intervention is required. However, currently available diagnostic approaches can only assess the level of inflammation, but not the degree of fibrosis, limiting rational therapeutic management of Crohn's disease patients. Recently, prolyl endopeptidase fibroblast activating protein (FAP) has been functionally implicated in fibrotic tissue remodelling, indicating it as a promising target for detection of sites of fibrotic tissue remodelling. Thus, intestinal fibrosis might be visualized using Gallium-68 labelled inhibitors of FAP (FAPI). While F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT is a standard diagnostic tool for visualizing inflammatory processes, we combined Ga-68-FAPI-46-PET/CT and F-18-FDG-PET/CT to differentiate predominantly fibrotic or inflammatory areas in Crohn's disease patients with ileo-colonic strictures., Methods: In our study, we analysed three Crohn's disease patients with anastomotic ileo-colonic strictures who underwent both dynamic Ga-68-FAPI-46-PET/CT and static F-18-FDG-PET/CT imaging to assess the level of visualized fibrotic areas within the stricture and differentiate it from inflammatory ones. PET images were analysed both visually and quantitatively. Furthermore, conventional MR enterography and endoscopy were performed in parallel to correlate observed findings. Two of the included patients underwent surgery and the histological specimen were analysed for the level of inflammation and fibrosis, which results were similarly compared to the findings of the PET imaging procedures., Results: Different uptake patterns of Ga-68-FAPI-46 could be observed in the anastomotic ileo-colonic strictures of the examined Crohn's disease patients, respectively. Immunohistochemical analyses demonstrated that there was a correlation between the level of Ga-68-FAPI-46 uptake and severity of fibrosis, while FDG uptake correlated with the inflammatory activity in the analysed strictures., Discussion: The combination with F-18-FDG-PET/CT represents a promising imaging modality to distinguish inflammation from fibrosis and guide subsequent therapy in stricturing Crohn's disease patients, warranting further studies., Competing Interests: M.F.N. has served as a speaker, or consultant, or received research grants from AbbVie, MSD, Takeda Pharma, Boehringer, Roche, Pfizer, Janssen, Pentax, PPD. R.A. has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AstraZeneca, Bristol-Myers Squibb, Celltrion Healthcare, Galapagos, Janssen-Cilag, Lilly, MSD Sharp and Dohme, Pfizer, Takeda Pharma. DFG-SFB/TRR241 Project No. C02 and IBDome (R.A.) are funded by the German Research Council (DFG). A.A. is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 493624887 (Clinician Scientist Program NOTICE). All other authors declare no conflict of interest., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Right heart failure (RHF) is a complication of pulmonary hypertension (PH) and increases the mortality independently of the underlying disease. However, the process of RHF development and progression is not fully understood. We aimed to develop effective approaches for early diagnosis and precise evaluation of RHF., Methods: Right ventricle (RV) pressure overload was performed via pulmonary artery banding (PAB) surgery in Sprague-Dawley (SD) rats to induce RHF. Echocardiography, right heart catheterization, histological staining, fibroblast activation protein (FAP) immunofluorescence and 18  F-labelled FAP inhibitor-42 ([ 18  F] -FAPI-42) positron emission tomography/computed tomography (PET/CT) were performed at day 3, week 1, 2, 4 and 8 after PAB. RNA sequencing was performed to explore molecular alterations between PAB and sham group at week 2 and week 4 after PAB respectively., Results: RV hemodynamic disorders were aggravated, and RV function was declined based on right heart catheterization and echocardiography at week 2, 4 and 8 after PAB. Progressive cardiac hypertrophy, fibrosis and capillary rarefaction could be observed in RV from 2 to 8 weeks after PAB. RNA sequencing indicated 80 upregulated genes and 43 downregulated genes in the RV at both week 2 and week 4 after PAB; Gene Ontology (GO) analysis revealed that fibrosis as the most significant biological process in the RV under pressure overload. Immunofluorescence indicated that FAP was upregulated in the RV from week 2 to week 8 after PAB; and [ 18  F] -FAPI-42 PET/CT revealed FAPI uptake was significantly higher in RV at week 2 and further increased at week 4 and 8 after PAB., Conclusion: RV function is progressively declined with fibrosis as the most prominent molecular change after pressure overload, and [ 18  F] -FAPI-42 PET/CT is as sensitive and accurate as histopathology in RV fibrosis evaluation., (© 2023. The Author(s).)

Computed tomography (CT), MR imaging, and PET with fluorodeoxyglucose F18/CT are commonly used for radiation therapy planning; however, issues including precise nodal staging on CT or false positive results on PET/CT limit their usability. Clinical trials using fibroblast activation protein ligands for additional imaging have provided promising results regarding staging and target volume delineation-particularly suitable for sarcoma, some gastrointestinal tumors, head and neck tumors, and lung and pancreatic cancer. Although further prospective trials are necessary to identify clinical settings for its application in radiation oncology, fibroblast activation protein inhibitor PET/CT indisputably represents an excellent opportunity for assisting radiotherapy planning., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A fibroblast activation protein (FAP) is an atypical type II transmembrane serine protease with both endopeptidase and post-proline dipeptidyl peptidase activity. FAP is overexpressed in cancer-associated fibroblasts (CAFs), which are found in most epithelial tumors. CAFs have been implicated in promoting tumor cell invasion, angiogenesis and growth and their presence correlates with a poor prognosis. However, FAP can generally be found during the remodeling of the extracellular matrix and therefore can be detected in wound healing and benign diseases. For instance, chronic inflammation, arthritis, fibrosis and ischemic heart tissue after a myocardial infarction are FAP-positive diseases. Therefore, quinoline-based FAP inhibitors (FAPIs) bind with a high affinity not only to tumors but also to a variety of benign pathologic processes. When these inhibitors are radiolabeled with positron emitting radioisotopes, they provide new diagnostic and prognostic tools as well as insights into the role of the microenvironment in a disease. In this respect, they deliver additional information beyond what is afforded by conventional FDG PET scans that typically report on glucose uptake. Thus, FAP ligands are considered to be highly promising novel tracers that offer a new diagnostic and theranostic potential in a variety of diseases.