Fluorodeoxyglucose cell incorporation as an index of cell proliferation: evaluation of accuracy in cell culture

Abstract

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 anticancer therapy. FDG cell incorporation reflects glycolytic activity whereas inhibition of cell proliferation corresponds to an efficient cancer treatment. The relationship between FDG incorporation and cell proliferation has yet to be demonstrated. Therefore, we aimed to correlate the effects of the toxic agents bleomycin and unlabelled meta-iodobenzylguanidine (mIBG) on cellular metabolism and proliferation. We determined the in vitro metabolic and cytotoxic effects of bleomycin and mIBG by measuring the incorporation of fluorine-18 FDG (%UFDG) and hydrogen-3 thymidine (%UTHY) in cells of the human premonocytic line U937 in the presence of increasing concentrations of these agents. Proliferation rate of these cells was studied by means of limiting dilution analysis. %UTHY appeared more sensitive to bleomycin or mIBG-mediated cell injury than %UFDG. After 1 h of exposure to 0.5 microM bleomycin, %UTHY was significantly reduced to 62.0% +/- 10.4% of control value whereas %UFDG remained unchanged (91.6% +/- 5.3%). Similar results were obtained after 1 h of exposure to increasing concentrations of mIBG (1 microM to 1 mM). After 20 h of exposure to bleomycin, %UTHY and %UFDG were significantly reduced as a function of concentration. After 20 h of exposure to mIBG, a transient increase in %UFDG up to 149.3% +/- 11.2% with 50 microM mIBG was further followed by a reduction to 20.1% +/- 6.7% with 0.5 mM (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)