Pushing the limits of molecular imaging. Learn more about MILabs’ Series 5 multi-modality PET/SPECT/OI/CT platforms offering <0.15 mm SPECT resolution and <0.6 mm PET resolution. The Series 5 systems feature hybrid nuclear and optical imaging, with unmatched morphological 4D CT capabilities.
Acute infections caused by dengue virus (DENV) and other members of the flavivirus genus, such as Zika virus, Japanese encephalitis virus, West Nile virus, and yellow fever virus, pose a significant threat to global public health. As the global burden of diseases such as dengue continues to rise, with nearly 400 million infections each year and more than two-thirds of the world’s population at risk of infection, therapeutic interventions are urgently required (1). Unfortunately, there have been no biomarkers that can sensitively distinguish viral load reduction due to innate cellular antiviral response from the viral load reduction due to antiviral drug-mediated mechanisms, thus significantly hampering the development of new antiviral drugs (2). Therefore, there is an urgent need to develop translational clinical platforms that will allow further understanding of disease pathophysiology.
In this scientific publication, researchers at Duke-NUS in Singapore demonstrate that high resolution whole-body PET/CT imaging of 18F-FDG with MILabs VECTor PET/SPECT/CT enables the sensitive detection of inflammatory disease foci in dengue-infected mice and that 18F-FDG can be used as a biomarker for quantifying disease response to treatment.
18F-FDG as an inflammation biomarker for imaging dengue virus infection
and treatment response Chacko et al., JCI Insight. 2(9):e93474. (2017)
Increased inflammation in the spleen, and small and large intestines of dengue-infected mice can be observed using positron emission tomography (PET), paired with the glucose metabolism probe, fluorodeoxyglucose (FDG) [middle], with the inflammation subsiding after antivirals were given [right]
MILabs’ high-resolution VECTor PET/SPECT/CT system is used to:
Image the whole-body of mice at sub-mm PET resolution in order to quantify 18F-FDG uptake in foci in the abdomen, including the S.Int., L.Int., spleen, and mesentery.
Monitor DENV-mediated inflammation in vivo and assess the efficacy of novel therapeutic compounds that can directly target the major tissues involved in dengue pathogenesis.
Demonstrate for the first time that the quantifiable reduction in intestinal 18F-FDG uptake by PET/CT imaging can be used to non-invasively and robustly define inflammation reduction as a surrogate endpoint for drug efficacy during preclinical development and clinical validation.
Show a significant temporal trend in 18F-FDG uptake in intestines and selected tissues and that sub-mm resolution PET robustly differentiated treatment-naive groups from drug-treated infected mouse groups.
Illustrate that high resolution whole-body PET/CT imaging of 18F-FDG may have a profound effect on reducing the high costs of drug discovery for emerging infectious diseases through reducing trial size and fast tracking of the drug development process.
Related Publications 1. Guzman MG, Harris E. Dengue. Lancet. 2015; 385(9966):453–465.
2. Sung C, et al. Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients. PLoS Negl Trop Dis. 2016;10(8): e0004851.