Inflammatory bowel disease (IBD) represents a collection of chronic, inflammatory diseases of the gastrointestinal tract. The overall prevalence of IBD is 396 cases per 100,000 persons per year, according to the CDC. These diseases can have a significant negative impact on the quality of life, especially in times of remission and relapse. There is a lack of research into the symptoms of IBD and many patients with IBD have to undergo constant surveillance to ensure the disease is being effectively managed.
The standard diagnostic technique for IBD, a disease of the gastrointestinal tract characterized by chronic relapsing and remitting inflammation, relies on endoscopy. This technique is considered invasive, features limitations in its ability to reach all areas of the small intestine, and it does not offer the physician any information as to specific mediators of the disease.
Innate Immunity Plays a Key Pathogenic Role in IBD
In IBD, inflammation is linked to the activation of the innate immune system. Colitis, an IBD, has been previously detected by immuno-positron emission tomography (PET) techniques. Considering IBD flares are often associated with increased activation of innate immune pathways, a study recently compared immuno-PET of antibodies to IL-1β, an inducible cytokine, and CD11b, a pan-myeloid innate immune marker, versus standard 18F-FDG and magnetic resonance imaging (MRI) approaches for detecting colonic inflammation in murine models. In this study, the researchers found that immuno-PET directed against innate immune cells and mediators may help detect colitis, at least in animals.
Study Tests Utility of Immuno-PET for IBD Identification and Monitoring
Australian researchers obtained colonic concentrations of IL-1β and myeloperoxidase (MPO) in a murine model. Using ELISA, colonic infiltration by CD11b+ CD3-innate immune cells were compared between healthy mice and mice with colitis. The researchers performed PET of 89Zr-labelled α-IL-1β and α-CD11b. They compared 18F-FDG by volume of interest with MRI by region of interest analysis.
Mice underwent a benchtop MRI scan using Bruker Biospin’s ICON™ MRI platform, a cryogen-free compact, permanent magnet bench-top MRI system for molecular and preclinical MRI in rats and mice. Additionally, PET experiments were performed over 15-minute periods using Bruker’s ALBIRA PET-single photon emission computed tomography small animal scanner. This scanner features a complete range of animal beds and monitoring accessories as well as a motorized animal handling system that enables accurate animal positioning and automatic co-registration of images.
In this model, colonic inflammation correlated with impaired colonic epithelial barrier permeability. Also, colonic inflammation was associated with increased CD11b+ CD3- innate immune cell infiltration into the colon as well as an increase in colonic concentrations of IL-1β and MPO. Colonic inflammation was detected by both Zr-α-IL-1β and Zr-α-CD11b immuno-PET. According to the researchers, F-FDG and all PET tracers were found to be more sensitive than MRI.
Colonic innate immune infiltration was increased in DSS colitis murine models, with many of the mice showing an approximately 7.5-fold increase in colonic MPO activity (P <.001). Additionally, these mice had an approximately 2.5-fold increase in colonic concentration of IL-1β (P <.01). These findings, according to the researchers, indicate that innate immune mediators are increased in mice with colitis.
There was no correlation between Zr-α-CD11b immuno-PET or MRI with colitis severity; however, F-FDG volume of interests did correlate with colitis severity. The researchers suggest these findings may relate to immunological processes that underly the innate immune activation observed in the disease. There was also a strong trend toward the correlation between Zr-α-IL-1β and colitis severity. The researchers found the distribution of Zr-α-IL-1β to be mainly located in the gastrointestinal tract, whereas Zr-α-CD11b was mostly distributed in more tissue types, including the spleen (P <.05), liver (P <.05), and bone marrow (P <.05).
Dextran sodium sulphate (DSS), which was used in this study to induce colitis, is associated with epithelial damage and infiltration of CD11b-expressing cells and increased concentrations of innate immune secreted IL-1β in the colon. These two mediators were reliably detected by PET in this study. The study was the first of its kind to highlight the potential of the radiolabeled antibodies against innate immune markers in the use of PET in the diagnosis and monitoring of IBD.
According to the researchers, the use of immuno-PET for IBD is limited by the large sizes of antibodies as well as challenges associated with tissue penetration in IBD. Despite these limitations, they suggest immuno-PET may offer clinical utility for diagnosing and monitoring IBD. The benefits of this may be particularly pronounced in patients who are difficult to scope, such as children with IBD and patients with either inflamed and/or fibrotic regions found in the small intestine.
- Centers for Disease Control and Prevention. Inflammatory bowel disease (IBD). https://www.cdc.gov/ibd/#epidIBD. Accessed February 27, 2020.
- Dmochowska N, Tieu W, Keller MD, et al. Immuno-PET of innate immune markers CD11b and IL-1β detects inflammation in murine colitis. J Nucl Med. 2019;60(6):858-863.
- Bruker. ICON. https://www.bruker.com/products/mr/preclinical-mri/icon.html. Accessed February 27, 2020.
- Bruker. ALBIRA. https://www.bruker.com/products/preclinical-imaging/nuclear-molecular-imaging/pet-spect-ct.html. Accessed February 27, 2020.