Immuno-PET of Innate Immune Markers CD11b and IL-1β Detects Inflammation in Murine Colitis

Abstract

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 ¹⁸F-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 ⁸⁹Zr-lα-IL-1β, ⁸⁹Zr-α-CD11b, and ¹⁸F-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. ⁸⁹Zr-α-IL-1β and ⁸⁹Zr-α-CD11b immuno-PET detected colonic inflammation, as did ¹⁸F-FDG, and all PET tracers were more sensitive than MRI. Although ¹⁸F-FDG volumes of interest correlated with colitis severity and a strong trend was observed with ⁸⁹Zr-α-IL-1β, no correlation was observed for ⁸⁹Zr-α-CD11b or MRI. ⁸⁹Zr-α-IL-1β was distributed mainly to the gastrointestinal tract, whereas ⁸⁹Zr-α-CD11b was distributed to more tissue types. Conclusion: Immuno-PET using antibodies directed to innate immune markers detected colonic inflammation, with ⁸⁹Zr-α-IL-1β providing a more tissue-specific signal than ⁸⁹Zr-α-CD11b. Development of these technologies for human subjects will potentially provide a less invasive approach than endoscopy for diagnosing and monitoring IBD.