The effect of PPAR-γ agonist on 18F-FDG PET imaging for differentiating tumors and inflammation lesions

Abstract

Introduction18F-2-deoxy-2-fluoro-d-glucose (18F-FDG) positron emission tomography (PET) has been used for imaging human cancers for several decades. Despite its extensive use, 18F-FDG PET imaging has limitations in the tumor findings. The goal of this study was to investigate the potential of a PPAR-γ agonist pioglitazone (PIO) to distinguish tumors and inflammatory lesions in 18F-FDG PET imaging. MethodsStudies of cellular uptake of 18F-FDG and Western blot were performed in macrophage (RAW264.7) and three tumor cell lines (A549, KB, and MDA-MB-231) after treatment with PIO. In vivo microPET/CT imaging and biodistribution were performed in animal models. ResultsThe uptake of 18F-FDG in the macrophages was decreased and uptake of 18F-FDG in the tumor cells was increased when these cells were treated with PIO. Western blot showed that the expression of Glut1 was reduced by treatment of PIO in the macrophage cells, whereas the expression of Glut1 in the tumor cells was increased. In vivo PET/CT imaging revealed that 18F-FDG uptake (%ID/g) in the tumors was enhanced from 4.05±1.46 to 5.28±1.92 for A549, from 3.9±0.5 to 4.9±0.2 for KB, and from 9.14±0.86 to 13.48±2.07 for MDA-MB-231 tumors after treatment with PIO. Unlike tumors, the RAW264.7 xenograft model showed the reduced 18F-FDG uptake in the inflammatory lesion from 11.74±1.19 to 6.50±1.47. The results of biodistribution also showed that 18F-FDG uptake in the tumors were increased after treatment of PIO. However, the uptake of inflammation lesions was reduced. ConclusionsIn this study, we demonstrated the effect of a PPAR-γ agonist PIO on 18F-FDG uptake in tumors and inflammation in vitro and in vivo. PIO has potential to differentiate tumors and inflammatory lesions on 18F-FDG PET imaging.