Differentiation of tumour and inflammation:: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells

Differentiation of tumour and inflammation:: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells
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DOI:
10.1007/s00259-005-0047-5
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发表时间:
2006-08-01
影响因子:
9.1
通讯作者:
Senekowitsch-Schmidtke, Reingard
Senekowitsch-Schmidtke, Reingard
中科院分区:
医学1区
文献类型:
--
作者:
Stoeber, Barbara;Tanase, Ursula;Senekowitsch-Schmidtke, Reingard

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目的:既往研究表明,放射性标记氨基酸在鉴别肿瘤和炎症方面可能优于FDG,其鉴别诊断价值可能比FDG高上级。因此,本研究的目的是探讨人体肿瘤和炎症细胞的FET和MET的摄取,并探讨其摄取kinetic.Methods:摄取研究,细胞孵育与370 kBq FET或3.7 kBq MET为15分钟。动力学研究进行了在不同浓度的FET和MET。结果:所有炎性细胞均比肿瘤细胞掺入更多的MET。相反,所有炎症细胞中的FET摄取均显著低于肿瘤细胞。在肿瘤细胞中,MET的摄取约为FET摄取的五倍。竞争性抑制剂在肿瘤细胞中将两种示踪剂的摄取减少到20-40%,在炎症细胞中减少到70%。动力学研究表明,MET和FET的运输是饱和的,在除巨噬细胞的所有细胞,并遵循米氏动力学。在粒细胞中观察到MET摄取的最高容量(V-max)和亲和力(K-m)。在DHL-4 cells.Conclusion:与MET相反,FET在肿瘤细胞中的积累程度明显大于炎症细胞。肿瘤和炎症细胞之间关于FET和MET摄取的显著差异表明FET和MET是L系统不同亚型的底物。
Purpose: Previous studies suggest that radiolabelled amino acids could be superior to FDG in differentiating tumour and inflammation. Therefore the aim of this study was to investigate the uptake of FET and MET in human tumour and inflammatory cells and to investigate their uptake kinetics.Methods: For uptake studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic studies were performed at variable concentrations of FET and MET. Competitive inhibition studies were done with BCH, MeAIB and L-serine.Results: All inflammatory cells incorporated more MET than the tumour cells. The uptake of FET, in contrast, was significantly lower in all inflammatory cells than in the tumour cells. In tumour cells the uptake of MET was about five times the uptake of FET. The competitive inhibitors reduced uptake of both tracers to 20-40% in tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET and FET transport was saturable in all cells except macrophages and followed a Michaelis-Menten kinetic. Highest capacity (V-max) and affinity (K-m) for the uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake were highest in the DHL-4 cells.Conclusion: In contrast to MET, FET accumulated to a significantly greater extent in tumour cells than in inflammatory cells. The marked differences between tumour and inflammatory cells concerning FET and MET uptake suggest that FET and MET are substrates of different subtypes of the L system.