No abstract

Inflammatory bowel disease (IBD), which includes both Crohn disease and ulcerative colitis, is a relapsing inflammatory disease of the gastrointestinal tract. Long-term chronic inflammatory conditions elevate the patient's risk of colorectal cancer (CRC). Currently, diagnosis requires endoscopy with biopsy. This procedure is invasive and requires a bowel-preparatory regimen, adding to patient burden. Interleukin 12 (IL12) and interleukin 23 (IL23) play key roles in inflammation, especially in the pathogenesis of IBD, and are established therapeutic targets. We propose that imaging of IL12/23 and its p40 subunit in IBD via immuno-PET potentially provides a new noninvasive diagnostic approach. Methods: Our aim was to investigate the potential of immuno-PET to image inflammation in a chemically induced mouse model of colitis using dextran sodium sulfate by targeting IL12/23p40 with a 89 Zr-radiolabeled anti-IL12/23p40 antibody. Results: High uptake of the IL12/23p40 immuno-PET agent was exhibited by dextran sodium sulfate-administered mice, and this uptake correlated with increased IL12/23p40 present in the sera. Competitive binding studies confirmed the specificity of the radiotracer for IL12/23p40 in the gastrointestinal tract. Conclusion: These promising results demonstrate the utility of this radiotracer as an imaging biomarker of IBD. Moreover, IL12/23p40 immuno-PET can potentially guide treatment decisions for IBD management.

Background and aimsInflammatory bowel disease (IBD), which includes both Crohn’s Disease (CD) and ulcerative colitis (UC), is a relapsing inflammatory disease of the gastrointestinal (GI) tract. Long term chronic inflammatory conditions elevate patients’ risk for colorectal cancer (CRC). Currently, diagnosis requires endoscopy with biopsy. This procedure is invasive and requires bowel preparatory regimen, adding to patient burden. Interleukin 23 (IL23) plays a key role in inflammation especially in the pathogenesis of IBD and is an established therapeutic target. We propose that imaging of IL23 via immunopositron emission tomography (immunoPET) will potentially lead to a new non-invasive diagnostic approach.MethodsThe aim of the present study is to investigate the potential of immunoPET to image inflammation in a chemically induced mouse model of colitis using dextran sodium sulfate (DSS) by targeting IL23 via its p40 subunit with a89Zr-radiolabeled α-IL23p40 antibody.ResultsHigh uptake of the IL23p40 immunoPET agent in mice were displayed in DSS-administered mice, which correlated with increased IL23p40 present in sera. Competitive binding studies confirmed the specificity of the radiotracer for IL23p40 in the GI tract.ConclusionTaken together, these promising results set the stage for developing this radiotracer as an imaging biomarker for IBD diagnosis. Noninvasive imaging of IBD with IL23p40 immunoPET may help physicians in their treatment decisions for IBD management.