Total-Body Multiparametric PET Quantification of ¹⁸ F-FDG Delivery and Metabolism in the Study of Coronavirus Disease 2019 Recovery

Abstract

Conventional whole-body static ¹⁸F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric ¹⁸F-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). <b>Methods:</b> The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic ¹⁸F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue ¹⁸F-FDG delivery rate <math xmlns="http://www.w3.org/1998/Math/MathML" id="ie1" display="inline" overflow="scroll"><mrow><msub><mrow><mi>K</mi></mrow><mn>1</mn></msub></mrow></math> and the phosphorylation rate <i>k</i>₃, as well as the macroparametric ¹⁸F-FDG net influx rate (<math xmlns="http://www.w3.org/1998/Math/MathML" id="ie2" display="inline" overflow="scroll"><mrow><msub><mrow><mi>K</mi></mrow><mi mathvariant="normal">i</mi></msub></mrow></math>). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. <b>Results:</b> We detected no significant difference in lung SUV but significantly higher lung SUVR and <math xmlns="http://www.w3.org/1998/Math/MathML" id="ie3" display="inline" overflow="scroll"><mrow><msub><mrow><mi>K</mi></mrow><mi mathvariant="normal">i</mi></msub></mrow></math> in COVID-19 recovery, indicating 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 <i>k</i>₃ but not with <math xmlns="http://www.w3.org/1998/Math/MathML" id="ie4" display="inline" overflow="scroll"><mrow><msub><mrow><mi>K</mi></mrow><mn>1</mn></msub></mrow></math>, which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow ¹⁸F-FDG metabolism measured with SUV, SUVR, and <math xmlns="http://www.w3.org/1998/Math/MathML" id="ie5" display="inline" overflow="scroll"><mrow><msub><mrow><mi>K</mi></mrow><mi mathvariant="normal">i</mi></msub></mrow></math> but a significantly higher bone marrow <math xmlns="http://www.w3.org/1998/Math/MathML" id="ie6" display="inline" overflow="scroll"><mrow><msub><mrow><mi>K</mi></mrow><mn>1</mn></msub></mrow></math> in the COVID-19 group, suggesting a difference in glucose delivery. Vaccinated COVID-19 subjects had a lower lung <math xmlns="http://www.w3.org/1998/Math/MathML" id="ie7" display="inline" overflow="scroll"><mrow><msub><mrow><mi>K</mi></mrow><mi mathvariant="normal">i</mi></msub></mrow></math> and a higher spleen <math xmlns="http://www.w3.org/1998/Math/MathML" id="ie8" display="inline" overflow="scroll"><mrow><msub><mrow><mi>K</mi></mrow><mi mathvariant="normal">i</mi></msub></mrow></math> than unvaccinated COVID-19 subjects. <b>Conclusion:</b> Higher lung glucose metabolism and bone marrow glucose delivery were observed with total-body multiparametric ¹⁸F-FDG PET in recovering COVID-19 subjects than in healthy subjects, implying continued inflammation during recovery. Vaccination demonstrated potential protection effects. Total-body multiparametric PET of ¹⁸F-FDG can provide a more sensitive tool and more insights than conventional whole-body static ¹⁸F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.