Tumor lactate content predicts for response to fractionated irradiation of human squamous cell carcinomas in nude mice

被引:158
作者
Quennet, Verena
Yaromina, Ala
Zips, Daniel
Rosner, Andrea
Walenta, Stefan
Baumann, Michael
Mueller-Klieser, Wolfgang
机构
[1] Johannes Gutenberg Univ Mainz, Inst Physiol & Pathophysiol, D-55128 Mainz, Germany
[2] Tech Univ Dresden, Dept Radiat Oncol, D-8027 Dresden, Germany
[3] Tech Univ Dresden, Expt Ctr, D-8027 Dresden, Germany
[4] Tech Univ Dresden, OncoRay Ctr Radiat Res Oncol, D-8027 Dresden, Germany
关键词
lactate imaging; human tumor xenografts; fractionated irradiation; local tumor control; head and neck squamous cell carcinomas;
D O I
10.1016/j.radonc.2006.08.012
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background and purpose: The present study was performed to test the hypothesis that lactate accumulation correlates with the radioresistance of malignant tumors due to the radical scavenging capacity of lactate or metabolic intermediates of glycolysis, such as pyruvate. Materials and methods: Five human head and neck squamous cell carcinoma cell lines (HNSCCs) xenografted in nude mice were treated with a clinically relevant irradiation protocol with 30 fractions within 6 weeks. The radiation dose necessary to locally control 50% of the tumors (TCD50) ranged from 47.4 to 129.8 Gy. Concentrations of glucose, lactate, and ATP in viable tumor regions as potential indicators of glycolytic activity were assessed with structure-associated quantitative bioluminescence imaging. Results: Mean lactate concentrations of the different tumor cell lines were in the range of 7.3-25.9 mu mol/g. TCD50 values were positively correlated with tumor lactate levels (R = 0.9824, p = 0.0028). Conclusions: The data obtained support the hypothesis that tissue lactate content correlates with radioresistance in solid human tumors. Furthermore, the results suggest that tumor lactate content determined non-invasively by proton magnetic resonance spectroscopy imaging may be used to predict for radioresistance of malignancies in the clinic; the data also imply that transient inhibition of glycolysis during treatment might possibly sensitize tumors to irradiation. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:130 / 135
页数:6
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