FLUORODEOXYGLUCOSE CELL INCORPORATION AS AN INDEX OF CELL-PROLIFERATION - EVALUATION OF ACCURACY IN CELL-CULTURE

The use of fluorodeoxyglucose (FDG) and positron emission tomography ( PET) is recognized as an accurate tool for the specific diagnosis and staging of cancer. It has also been proposed for the monitoring of ant icancer therapy. FDG cell incorporation reflects glycolytic activity w hereas inhibition of cell proliferation corresponds to an efficient ca ncer treatment. The relationship between FDG incorporation and cell pr oliferation has yet to be demonstrated. Therefore, we aimed to correla te the effects of the toxic agents bleomycin and unlabelled meta-iodob enzylguanidine (mIBG) on cellular metabolism and proliferation. We det ermined the in vitro metabolic and cytotoxic effects of bleomycin and mIBG by measuring the incorporation of fluorine-18 FDG (%U(FDG)) and h ydrogen-3 thymidine (%U(THY)) in cells of the human premonocytic line U937 in the presence of increasing concentrations of these agents. Pro liferation rate of these cells was studied by means of limiting diluti on analysis. %U(THY) appeared more sensitive to bleomycin or mIBG-medi ated cell injury than %U(FDG), After 1 h of exposure to 0.5 muM bleomy cin, %U(THY) was significantly reduced to 62.0% +/- 10.4% of control v alue whereas %U(FDG) remained unchanged (91.6% +/- 5.3%). Similar resu lts were obtained after 1 h of exposure to increasing concentrations o f mIBG (1 muM to 1 mM). After 20 h of exposure to bleomycin, %U(THY) a nd %U(FDG) were significantly reduced as a function of concentration. After 20 h of exposure to mIBG, a transient increase in %U(FDG) up to 149.3% +/- 11.2% with 50 muM mIBG was further followed by a reduction to 20.1% +/- 6.7% with 0.5 mM (P<0.001). The clonogenic efficiency was reduced as a function of bleomycin (ANOVA, n=255, P) or mIBG concentr ation (n=80, P) and nearly abolished with 0.1 muM bleomycin or 0.1 mM mIBG. In conclusion, %U(THY) appears to be a more sensitive index of c ytotoxicity in vitro and more accurately relates to cell proliferation than %U(FDG).