Total-Body Multiparametric PET Quantification of (18)F-FDG Delivery and Metabolism in the Study of COVID-19 Recovery

Conventional whole-body (18)F-FDG PET imaging provides a semi-quantitative evaluation of overall glucose metabolism without gaining insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric (18)F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). METHODS: The study included thirteen healthy subjects and twelve recovering COVID-19 subjects within eight weeks of confirmed diagnosis. Each subject had a dynamic (18)F-FDG scan on the uEXPLORER total-body PET/CT system for one hour. Semiquantitative standardized uptake value (SUV) and SUV ratio relative to blood (SUVR) were calculated for regions of interest (ROIs) in different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify microparametric rate constants [Formula: see text] and [Formula: see text] that characterize (18)F-FDG blood-to-tissue delivery and intracellular phosphorylation, respectively, and a macroparameter [Formula: see text] that represents (18)F-FDG net influx rate. Statistical tests were performed to examine differences between the healthy controls and recovering COVID-19 subjects. Impact of COVID-19 vaccination was investigated. We further generated parametric images to confirm the ROI-based analysis. RESULTS: We detected no significant difference in lung SUV but significantly higher lung SUVR and [Formula: see text] in the recovering COVID-19 subjects, indicating an improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate [Formula: see text] , but not with the delivery rate [Formula: see text] , which suggests it is glucose phosphorylation, not glucose delivery, that drives the observed difference of glucose metabolism in the lungs. Meanwhile, there was no or little difference in bone marrow metabolism measured with SUV, SUVR and [Formula: see text] , but a significant increase in bone-marrow (18)F-FDG delivery rate [Formula: see text] in the COVID-19 group (p < 0.05), revealing a difference of glucose delivery in this immune-related organ. The observed differences were lower or similar in vaccinated COVID-19 subjects as compared to unvaccinated ones. The organ ROI-based findings were further supported by parametric images. CONCLUSIONS: Higher lung glucose metabolism and bone-marrow glucose delivery were observed with total-body multiparametric (18)F-FDG PET in recovering COVID-19 subjects as compared to healthy subjects, which suggests continued inflammation due to COVID-19 during the early stages of recovery. Total-body multiparametric PET of (18)F-FDG delivery and metabolism can provide a more sensitive tool and more insights than conventional static whole-body (18)F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.