New research in mice shows that immuno-positron emission tomography can accurately detect inflammatory bowel disease in a murine model and that the imaging technique can reveal specific details regarding mediators of inflammation.
Inflammatory bowel disease (IBD) is a chronic condition that affected approximately 3 million adults in the United States in 2015.
Usually, people with IBD experience symptoms that flare up and remit.
Some people are more at risk of developing the condition. Being born in the U.S., being part of certain sociodemographic groups, and being older than 45 are all factors that are likely to increase the risk of developing IBD.
New research, however, suggests that immuno-positron emission tomography (immuno-PET) can be a more effective means of diagnosing IBD. The new study appears in The Journal of Nuclear Medicine.
Patrick A. Hughes, Ph.D. — head of the Gastrointestinal Neuroimmune Interactions Research Group, which is part of the Centre for Nutrition and Gastrointestinal Disease Research at the University of Adelaide, in Australia — is the corresponding author of the paper.
Hughes explains the motivation for his and his colleagues’ research, saying that endoscopy “is invasive and does not provide real-time information regarding the role of specific mediators and drug targets.”
“There is a need to develop less invasive tools that provide quick diagnostic information for IBD,” the researcher continues.
“This is particularly relevant when the area of inflammation is beyond the reach of the endoscope, such as difficult-to-access regions of the small intestine and in patient populations that have increased risk in endoscopy, including [children] and [people with hemophilia].”
To study the potential of immuno-PET for diagnosing IBD, Hughes and colleagues used a mouse model of ulcerative colitis.
The inflammation of IBD is linked to the activation of the innate immune system. Innate immune cells have a cell surface receptor called CD11b and they secrete interleukin-1 beta (IL-1β) to create an immune response.
In the present study, Hughes and the team used “immuno-PET of antibodies to IL-1β and CD11B” to detect inflammation in the mice’s colons. They then compared the efficacy of this method with that of “standard 18F-FDG [PET scanning] and MRI approaches.”
In order to assess both of these scanning methods, the researchers examined the signs of colitis in the mice and compared them, every day, with a group of healthy age- and weight-matched mice.
Specifically, they looked at the shortening of the colon, the permeability of the epithelial barrier, and the loss of body weight. The scientists also measured IL-1β and CD11b levels, showing that mice with colitis had higher levels of these immune mediators.
The research revealed a strong positive correlation between weight loss and uptake of 18F-FDG in the distal colon using standard PET and a clear trend toward a similar positive correlation when they measured IL-1β using immuno-PET.
However, when they measured CD11b, they did not obtain the same results. And when the researchers used MRI to measure inflammation, they found no correlation with weight loss.
Additionally, the researchers performed an ex vivo analysis and found that the levels of IL-1β and CD11b, as measured with immuno-PET, were raised throughout the gastrointestinal tract in mice with colitis, but not in healthy mice. Also, IL-1β correlated with the severity of the condition, whereas CD11b did not.
“These findings are important for inflammatory diseases in general, as many of the biologics used to treat these diseases are directed against specific immune mediators,” says Hughes.
“However, these drugs are also associated with primary and secondary nonresponse,” he adds.
“Future refinements will lead to theranostic applications where the efficacy of drugs can be rapidly and noninvasively determined, leading to precision treatment not only in IBD but also in other inflammatory diseases.”
Patrick A. Hughes, Ph.D.