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Background: The combination of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) with magnetic resonance imaging (MRI) as integrated PET/MRI in one examination is a new cutting-edge technology for the non-invasive assessment of disease activity in patients with inflammatory bowel disease not accessible for routine diagnostic. In Crohns disease (CD) a manifestation throughout the gastrointestinal tract is possible. Therefore, a comprehensive diagnostic work-up including endoscopy and an extended exploration of the small intestine is recommended. Noninvasive biomarkers like Lactoferrin and Calprotectin are increasingly popular and used in all-day patient care. Aim: To compare the performance of non-invasive biomarkers to PET/MRI and colonoscopy in patient with CD with a special focus on small bowel involvement.Methods: In every patient, a PET/MRI including the maximum standardized uptake value ratio gut/liver (rSUV) and a colonoscopy including an endoscopy index (SES-CD) was performed. The PET/MRI was rated as pivotal for the small bowel and colonoscopy for the colon. Lactoferrin (LF; >7.25 μg/g; TechLab), CalprotectinIMUN (CalI; >50 μg/g; Immundiagnostik - monoclonal), CalprotectinCALPREST (CalP; >50 μg/g; Eurospital - polyclonal), PMN-elastasis (PMN-e; >0.062 μg/g; Immundiagnostik), S100A12 (Immundiagnostik) as well as CRP (≥0.5 mg/dl) were correlated to the SUVQuot and the SES-CD using nonparametric correlation analyses and median levels in active and inactive patient groups were calculated.Results: 50 patients (32 female), mean age 43.1±13.4 years (range 20–67) with known CD (mean years since first diagnosis 12.8±11.5) were included in the study. N=28 patients showed signs of active disease in colonoscopy and/or PET/MRI, n=14 patients showed at least one stenosis. N=17 patients showed exclusively small bowel involvement. rSUV range was 0.5–11.5, SES-CD median in active disease was 4.5 (range 0–12) indicating mild to moderate disease. rSUV was correlated significantly with the SES-CD (rs(45)=0.505; p<0.001) and with LF (r(50)=0.33; p=0.026) and S100A12 (r(50)=0.30; p=0.04), but not with PMN-e, CalP, CalI and CRP (all p>0.05). The median levels (inactive/active) of LF were: 3.5/9 μg/g, CalI: 96.3/122.4 μg/g, CalP: 195/238 μg/g; PMN-E: 0.115/0.15 μg/g, S100A12: 47.3/55.1 μg/g, CRP: 0.25/0.4 mg/dl. In the patient group with exclusively small bowel involvement rSUV was correlated significantly only with LF (r(50)=0.676; p=0.003).Conclusions: Lactoferrin and S100A12 levels were significantly correlated to rSUV and Lactoferrin levels remained significantly correlated to rSUV for exclusively small bowel activity. Further studies are warranted to assess the performance of fecal biomarkers in IBD identified by PET/MRI.