Inflammatory bowel disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown, but it is thought to involve a hypersensitive immune response to environmental antigens, including the microbiota. Diagnosis and monitoring of IBD is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) of inflammatory mediators, and how these developments may be applied to the microbiota.

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. The diagnosis and monitoring of IBD are reliant on endoscopy, which is invasive and does not provide information on specific mediators. Symptom flare in IBD is associated with increased activation of innate immune pathways. Immuno-PET approaches have previously demonstrated the ability to detect colitis; however, a direct comparison of antibodies targeted to innate immune mediators and cells has not been done. We aimed to compare immuno-PET of antibodies to IL-1β and CD11b against standard 18 F-FDG and MRI approaches to detect colonic inflammation. Methods: Colonic concentrations of IL-1β and myeloperoxidase were determined by ELISA, and colonic infiltration by CD11b-positive CD3-negative innate immune cells was determined by flow cytometry and compared between healthy and dextran sodium sulphate-treated colitic mice. PET of 89 Zr-lα-IL-1β, 89 Zr-α-CD11b, and 18 F-FDG was compared by volume-of-interest analysis and with MRI by region-of-interest analysis. Imaging results were confirmed by ex vivo biodistribution analysis. Results: Colonic inflammation was associated with impaired colonic epithelial barrier permeability, increased colonic IL-1β and myeloperoxidase concentrations, and increased CD11b-positive CD3-negative innate immune cell infiltration into the colon. 89 Zr-α-IL-1β and 89 Zr-α-CD11b immuno-PET detected colonic inflammation, as did 18 F-FDG, and all PET tracers were more sensitive than MRI. Although 18 F-FDG volumes of interest correlated with colitis severity and a strong trend was observed with 89 Zr-α-IL-1β, no correlation was observed for 89 Zr-α-CD11b or MRI. 89 Zr-α-IL-1β was distributed mainly to the gastrointestinal tract, whereas 89 Zr-α-CD11b was distributed to more tissue types. Conclusion: Immuno-PET using antibodies directed to innate immune markers detected colonic inflammation, with 89 Zr-α-IL-1β providing a more tissue-specific signal than 89 Zr-α-CD11b. Development of these technologies for human subjects will potentially provide a less invasive approach than endoscopy for diagnosing and monitoring IBD. Detects Inflammation inβ Immuno-PET of Innate Immune Markers CD11b and IL-1 http://jnm.snmjournals.org/content/60/6/858 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

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