Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells
Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells
复制标题
DOI：
10.1016/j.nucmedbio.2006.08.002
复制
发表时间：
2006-11-01
影响因子：
3.1
通讯作者：
DeGrado, Timothy R.
中科院分区：
文献类型：
--
作者：
Hara, Toshihiko;Bansal, Aditya;DeGrado, Timothy R.
简介：胆碱、醋酸盐和葡萄糖（[2-F-18]氟-2-脱氧葡萄糖，[F-18]FDG）类似物作为正电子发射断层扫描（PET）示踪剂用于前列腺癌的成像正在研究中;然而，它们对肿瘤缺氧的反应尚未阐明。在有氧或缺氧条件下，在雄激素依赖性PC-3细胞和雄激素敏感性LNCaP细胞中监测[甲基-H-3]胆碱、[1-C-14]乙酸盐和[F-18]FDG的摄取。结果：PC-3细胞的需氧胆碱和乙酸摄取比FDG摄取高5 ~ 6倍，而LNCaP细胞的胆碱摄取比乙酸摄取高2.2倍，比FDG摄取高10倍。缺氧4 h后，PC-3细胞FDG摄取增加85%，胆碱摄取减少15%，乙酸摄取增加36%，而LNCaP细胞FDG摄取增加212%，胆碱摄取减少28%，乙酸摄取无变化。结论：在有氧条件下，PC-3和LNCaP细胞对各种示踪剂的摄取均表现出胆碱>乙酸> FDG的顺序。在缺氧细胞中，顺序相反，反映了对缺氧的不同生化反应。这些发现可能有助于解释这些示踪剂在前列腺癌的不同阶段和位置的不同反应的PET成像结果。雄激素耗竭显著抑制了LNCaP细胞中所有三种示踪剂的摄取，这表明抗雄激素治疗后进行PET成像时可能低估了疾病状态。(c)2006年爱思唯尔公司All rights reserved.
Introduction: Choline, acetate and glucose ([2-F-18]fluoro-2-deoxyglucose, [F-18]FDG) analogs are under investigation as positron emission tomography (PET) tracers for the imaging of prostate cancer; however, their response to tumor hypoxia has not been clarified.Methods: The uptake of [methyl-H-3]choline, [1-C-14]acetate and [F-18]FDG was monitored in androgen-in dependent PC-3 cells and androgen-sensitive LNCaP cells under aerobic or anoxic conditions. The effect of androgen depletion was also examined.Results: PC-3 cells exhibited aerobic choline and acetate uptake five to six times higher than FDG uptake, whereas LNCaP cells showed choline uptake 2.2-fold higher than acetate uptake and 10-fold higher than FDG uptake. After 4 h of anoxia, PC-3 cells showed an 85% increase in FDG uptake, a 15% decrease in choline uptake and a 36% increase in acetate uptake, whereas LNCaP cells showed a 212% increase in FDG uptake; a 28% decrease in choline uptake and no change in acetate uptake. Androgen depletion resulted in a marked decrease in the uptake of all tracers in LNCaP cells but no changes in PC-3 cells.Conclusion: In aerobic conditions, both PC-3 and LNCaP cells exhibited an order of uptake preference as follows: choline > acetate > FDG. In hypoxic cells, the order is reversed, reflecting diverse biochemical responses to hypoxia. These findings may help to explain PET imaging findings of the diverse responses of these tracers in different stages and locations of prostate cancer. Androgen depletion markedly suppressed the uptake of all three tracers in LNCaP cells, which suggests the potential for underestimation of the disease state when PET imaging is performed subsequent to antiandrogen therapy. (c) 2006 Elsevier Inc. All rights reserved.