The effect of PPAR-gamma agonist on (18)F-FDG uptake in tumor and macrophages and tumor cells.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Kim
Se-Lim
SL
Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712, Republic of Korea.
Kim
Eun-Mi
EM
Cheong
Su-Jin
SJ
Lee
Chang-Moon
CM
Kim
Dong Wook
DW
Jeong
Hwan-Jeong
HJ
Lim
Seok Tae
ST
Sohn
Myung-Hee
MH
Yim
Chang Yeol
CY
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D047495:PPAR gamma / Q000819:agonists*; D049268:Positron-Emission Tomography; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014057:Tomography, X-Ray Computed
D051246:Glucose Transport Proteins, Facilitative; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019788:Fluorodeoxyglucose F18; D006593:Hexokinase; D005947:Glucose; D004121:Dimethyl Sulfoxide