The effect of PPAR-γ agonist on 18F-FDG uptake in tumor and macrophages and tumor cells

Abstract

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors, and its role in adipogenesis and glucose metabolism has been well established. PPAR-gamma agonists have been shown to inhibit many cytokines and to have anti-inflammatory effects. In pathologic conditions, enhanced fluoro-2-deoxy-D-glucose (FDG) uptake is observed not only in malignant tumors but also in inflammatory lesions, and this uptake occurs through the glucose transporter in these cells. Thus, the present study was undertaken to investigate the potential of using PPAR-gamma's glucose uptake ability as a diagnostic tool to differentiate between macrophage and tumor cells. Cellular uptake studies were carried out on macrophage and two tumor cell lines for comparison by using (18)F-FDG. Western blot analysis was performed to determine the expression levels of both the glucose transporter and hexokinase protein. To confirm the possibility of differentiation between tumor and inflammatory lesions using rosiglitazone based on in vitro studies, (18)F-FDG (3.7 x 10(6) Bq) uptake in A549 and RAW 264.7 xenograft mice was compared. The cellular uptake study findings were quite different for macrophages and tumor cells. (18)F-FDG uptakes by macrophages decreased by about 60% but was increased twofold in tumor cells after rosiglitazone treatment. Moreover, the expressions of proteins related to glucose uptake correlated well with cellular glucose accumulation in both cell types. Higher tumor uptake was observed after the injection of rosiglitazone in A549 xenograft mice (1.58+/-0.55 to 4.66+/-1.16), but no significant change of (18)F-FDG uptake was shown in RAW 264.7 xenograft mice (4.04+/-1.16 to 4.00+/-0.14). The present study demonstrates the roles of PPAR-gamma agonist on FDG uptake in macrophages and tumor cells in vitro and in vivo. Our findings suggest that rosiglitazone has the potential to increase the contrast between tumor and inflammatory lesions.