Slosman D O, Pittet N, Donath A, Polla B S
Nuclear Medicine Division, University Hospital, Geneva, Switzerland.
Eur J Nucl Med. 1993 Nov;20(11):1084-8. doi: 10.1007/BF00173487.
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)
氟脱氧葡萄糖(FDG)和正电子发射断层扫描(PET)的应用被认为是癌症特异性诊断和分期的准确工具。它也被提议用于监测抗癌治疗。FDG细胞摄取反映糖酵解活性,而细胞增殖的抑制则对应于有效的癌症治疗。FDG摄取与细胞增殖之间的关系尚未得到证实。因此,我们旨在关联博来霉素和未标记的间碘苄胍(mIBG)这两种毒性药物对细胞代谢和增殖的影响。我们通过在这些药物浓度不断增加的情况下,测量人早幼粒细胞系U937细胞中氟 - 18 FDG的摄取率(%UFDG)和氢 - 3胸苷的摄取率(%UTHY),来确定博来霉素和mIBG的体外代谢和细胞毒性作用。通过有限稀释分析研究这些细胞的增殖率。%UTHY对博来霉素或mIBG介导的细胞损伤似乎比%UFDG更敏感。暴露于0.5微摩尔博来霉素1小时后,%UTHY显著降低至对照值的62.0%±10.4%,而%UFDG保持不变(91.6%±5.3%)。暴露于浓度不断增加的mIBG(1微摩尔至1毫摩尔)1小时后,也获得了类似结果。暴露于博来霉素20小时后,%UTHY和%UFDG随浓度显著降低。暴露于mIBG 20小时后,50微摩尔mIBG使%UFDG短暂增加至149.3%±11.2%,随后在0.5毫摩尔时降至20.1%±6.7%(P<0.001)。(摘要截短于250字)