Abstract
BackgroundRadiation pneumonitis is a common and potentially fatal complication of radiotherapy (RT). Some patients with radiation pneumonitis show increases in uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET), but others do not. The exact relationship between radiation pneumonitis and 18F-FDG PET findings remains controversial.MethodsWe used an animal model of radiation pneumonitis involving both radiation and simulated bacterial infection in Wistar rats. Treatment groups (10 rats/group) were as follows: control, RT-only, lipopolysaccharide (LPS)-only, and RT+LPS. All rats had micro-PET scans at 7 weeks after RT (or sham). Histologic, immunohistochemical, and biochemical analyses were performed to evaluate potential mechanisms.ResultsIrradiated rats had developed radiation pneumonitis at 7 weeks after RT based on pathology and CT scans. Maximum and mean standardized uptake values (SUVmax and SUVmean) at that time were significantly increased in the LPS group (P < 0.001 for both) and the RT+LPS group (P < 0.001 for both) relative to control, but were not different in the RT-only group (P = 0.156 SUVmax and P = 0.304 SUVmean). The combination of RT and LPS increased the expression of the aerobic glycolysis enzyme PKM2 (P < 0.001) and the glucose transporter GLUT1 (P = 0.004) in lung tissues. LPS alone increased the expression of PKM2 (P = 0.018), but RT alone did not affect PKM2 (P = 0.270) or GLUT1 (P = 0.989).ConclusionsAseptic radiation pneumonitis could not be accurately assessed by 18F-FDG PET, but was visualized after simulated bacterial infection via LPS. The underlying mechanism of the model of bacterial infection causing increased FDG uptake may be the Warburg effect.
Highlights
Radiation pneumonitis is a common and potentially fatal complication of radiotherapy (RT)
Pneumonitis and cytokine levels In the pre-experiment to determine the rat model of radiation pneumonitis, significant radiation pneumonitis was apparent on weekly micro-Computed tomography (CT) scans by 7 weeks after RT (Additional file 1: Fig. S2)
We did find elevated FDG uptake in rats given LPS, with or without RT, which we interpret as indicating that the model of bacterial infection simulated by LPS affects the normal glucose metabolism and uptake process via the Warburg effect, leading to upregulation of the expression of the GLUT1 glucose transporter on the cell membrane, which led to increased 18F-FDG uptake
Summary
Radiation pneumonitis is a common and potentially fatal complication of radiotherapy (RT). An imaging method that accurately detects radiation pneumonitis would be quite valuable, The advent of molecular and functional imaging and the relationship between these imaging modalities and radiation pneumonitis have been the subject of considerable research interest. One such approach involves 18F- fluorodeoxyglucose (FDG) positron emission tomography (PET), a nuclear medicine medical imaging technique in wide use for diagnosis and disease staging and response evaluation in a great number of cancers as well as in several inflammatory conditions [4,5,6].
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