A Comparison between Radiolabeled Fluorodeoxyglucose Uptake and Hyperpolarized 13C-Labeled Pyruvate Utilization as Methods for Detecting Tumor Response to Treatment
A Comparison between Radiolabeled Fluorodeoxyglucose Uptake and Hyperpolarized 13C-Labeled Pyruvate Utilization as Methods for Detecting Tumor Response to Treatment
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DOI：
10.1593/neo.09254
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发表时间：
2009-06-01
期刊：
影响因子：
4.8
通讯作者：
Brindle, Kevin M.
中科院分区：
文献类型：
--
作者：
Witney, Timothy H.;Kettunen, Mikko I.;Brindle, Kevin M.
对治疗的早期肿瘤反应的检测可以给出临床结果的指示。葡萄糖类似物[F-18] 2-氟-2-脱氧-D-葡萄糖（FDG）摄取的正电子发射断层扫描测量已证明其在临床中检测早期治疗反应的潜力。我们最近已经表明，C-13磁共振光谱和光谱成像测量的摄取和转换的超极化[1-C-13]丙酮酸[1-C-13]乳酸可用于检测治疗反应的小鼠淋巴瘤模型。本研究将这些磁共振测量结果与化疗后FDG摄取的变化进行比较。在体外肿瘤细胞和体内肿瘤中，发现FDG摄取的减少先于丙酮酸和乳酸之间的超极化C-13标记的通量的减少。然而，在药物治疗后24小时，FDG摄取的减少和丙酮酸-乳酸通量的减少的幅度是相当的。在细胞中，FDG摄取的减少与促进性葡萄糖转运蛋白的质膜表达变化相关，而丙酮酸-乳酸通量的减少可以通过聚（ADP-核糖）聚合酶活性的增加和随后NAD（H）库的耗尽来解释。这些结果表明，丙酮酸和乳酸之间的流量测量可能是一种替代FDG-正电子发射断层扫描成像肿瘤治疗反应在临床上。
Detection of early tumor responses to treatment can give an indication of clinical outcome. Positron emission tomography measurements of the uptake of the glucose analog, [F-18] 2-fluoro-2-deoxy-D-glucose (FDG), have demonstrated their potential for detecting early treatment response in the clinic. We have shown recently that C-13 magnetic resonance spectroscopy and spectroscopic imaging measurements of the uptake and conversion of hyperpolarized [1-C-13] pyruvate into [1-C-13] lactate can be used to detect treatment response in a murine lymphoma model. The present study compares these magnetic resonance measurements with changes in FDG uptake after chemotherapy. A decrease in FDG uptake was found to precede the decrease in flux of hyperpolarized C-13 label between pyruvate and lactate, both in tumor cells in vitro and in tumors in vivo. However, the magnitude of the decrease in FDG uptake and the decrease in pyruvate to lactate flux was comparable at 24 hours after drug treatment. In cells, the decrease in FDG uptake was shown to correlate with changes in plasma membrane expression of the facilitative glucose transporters, whereas the decrease in pyruvate to lactate flux could be explained by an increase in poly(ADP-ribose) polymerase activity and subsequent depletion of the NAD(H) pool. These results show that measurement of flux between pyruvate and lactate may be an alternative to FDG-positron emission tomography for imaging tumor treatment response in the clinic.