Authors: Martha Powell, Future Science Group
Collaborative research from Duke-NUS Medical School (NA, USA and Singapore) and Singapore General Hospital has uncovered a novel approach to imaging dengue infection. The approach, which uses positron emission tomography (PET), could present a non-invasive and real-time method to monitor infections in clinic and also monitor the effectiveness of treatments.
PET is commonly used to detect solid tumours; however, this study, published recently in JCI Insight, pioneered a new use that allowed them to visualize dengue infection in real-time.
During an infection with dengue virus, inflammation of the intestine is a common occurrence and corresponds with an increase in glucose uptake by intestinal cells. The team therefore utilized a fluorescent probe 18F- fluorodeoxyglucose (FDG) that, when combined with PET, highlights where glucose is being absorbed, allowing the team to visualize the location of inflammation and use this as a biomarker for infection.
The team assessed the novel approach in mouse models, discovering that during a dengue infection increased inflammation occurred in the spleen, large and small intestines of mice. They also demonstrated that uptake of FDG was correlated with traditional markers of infection – increased viral load and raised levels of proinflammatory cytokines. In addition, the team observed that levels of FDG decreased when the mice were treated with antivirals.
The researchers also discovered that tracking glucose uptake predicted both the progression and severity of dengue infection, demonstrating its applicability to a clinical setting. Not only could this new method be utilized to monitor patients, it could also be a useful tool to assess the effectiveness of novel treatments.
Author Jenny Low (Singapore General Hospital) explained: “Traditionally, in research, the amount of virus in the blood is measured and used as an indicator of disease severity. What makes the findings of this study so ground-breaking is that we may have a non-invasive way to track dengue infections in our patients more accurately during clinical trials to better measure if the experimental treatment given is effective.”
Senior author Subhash Vasudevan (Duke-NUS) added: “Being able to visualize dengue infection in the body potentially transforms how the effectiveness of new dengue therapeutics is assessed. We look forward to collaborating with academic and industry partners who are looking to validate their new dengue therapeutics using this novel approach.”
This novel dengue-associated inflammation biomarker could present a non-invasive and real-time method to track infections and more accurately assess new treatments. The next step is to investigate whether these findings in mice translatable in human patients through a clinical trial. The team is currently recruiting for this and hope that positive results could transform how we monitor infection.
First author Ann-Marie Chacko (Duke-NUS) concluded: “To our knowledge, this is the very first time PET has been systematically evaluated in the field of acute viral infectious diseases. We are excited to be able to repurpose this non-invasive technology, and generate such robust images of live dengue infection in the body.”
Sources: Chacko A, Watanabe S, Herr KJ et al. 18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response. JCI insight. doi:10.1172/jci.insight.93474 (Epub ahead of print) (2017); www.eurekalert.org/pub_releases/2017-06/dms-ana060517.php