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评估乳酸作为1H核磁共振波谱指数用于非侵入性预测和早期检测EMT6肿瘤对放射治疗的反应。

Evaluation of lactate as a 1H nuclear magnetic resonance spectroscopy index for noninvasive prediction and early detection of tumor response to radiation therapy in EMT6 tumors.

作者信息

Aboagye E O, Bhujwalla Z M, He Q, Glickson J D

机构信息

The Johns Hopkins University School of Medicine, Department of Radiology, Baltimore, Maryland 21205, USA.

出版信息

Radiat Res. 1998 Jul;150(1):38-42.

PMID:9650600
Abstract

In a recent study (Int. J. Radiat. Oncol. Biol. Phys. 36, 635-639, 1996), 1H nuclear magnetic resonance (NMR) spectroscopy was used to demonstrate significant decreases in lactate levels after gamma irradiation of radiosensitive RIF-1 tumors in vitro. For comparison, we have examined the effects of gamma radiation on lactate levels in the more radioresistant EMT6 tumor. Single-slice (5-6 mm thick) localized 1H spectra of subcutaneous RIF-1 (untreated) and EMT6 tumors (pretreatment, 24 and 48 h postirradiation with 4, 10 or 20 Gy of gamma radiation) were measured by the selective multiple quantum coherence transfer method (Sel-MQC, approximately 4 min acquisition time). Both pretreatment lactate levels and pretreatment lactate dehydrogenase (LDH) activities were found to be similar in RIF-1 and EMT6 tumors, suggesting that steady-state lactate levels are unlikely to be reliable indices for predicting response to radiation therapy. After 10 Gy gamma irradiation, EMT6 tumors showed a 21% decrease relative to pretreatment lactate levels at 48 h (1.04 +/- 0.22 to 0.82 +/- 0.16; P = 0.06); after 20 Gy a 40% decrease was observed at 48 h (1.34 +/- 0.27 to 0.81 +/- 0.10; P = 0.07). No significant changes in lactate levels were observed in control EMT6 tumors or in tumors treated with 4 Gy of gamma radiation, in contrast to changes detected previously in RIF-1 tumors, which showed a significant decrease in lactate by 48 h for both 2 and 4 Gy. The decreased effect of radiation on lactate levels in EMT6 compared to RIF-1 tumors may be attributed to the higher hypoxic fraction and lower radiosensitivity of EMT6 tumors (Int. J. Radiat. Oncol. Biol. Phys. 10, 695-712, 1984). The decrease in lactate levels did not, however, strictly reflect the extent of the response to therapy for the high dose of 20 Gy. This study together with our earlier study (Int. J. Radiat. Oncol. Biol. Phys. 36, 635-639, 1996) provides evidence to support the hypothesis that changes in steady-state tumor lactate levels may serve as sensitive early indices of tumor response to gamma radiation at doses of the order of 2 to 4 Gy.

摘要

在最近一项研究(《国际放射肿瘤学、生物学与物理学杂志》36卷,635 - 639页,1996年)中,利用氢核磁共振(NMR)光谱法证明,在体外对放射敏感的RIF - 1肿瘤进行伽马射线照射后,乳酸水平显著下降。为作比较,我们研究了伽马射线对放射抗性更强的EMT6肿瘤中乳酸水平的影响。通过选择性多量子相干转移方法(Sel - MQC,采集时间约4分钟)测量皮下RIF - 1(未治疗)和EMT6肿瘤(预处理、用4、10或20 Gy伽马射线照射后24小时和48小时)的单层面(5 - 6毫米厚)局部氢光谱。结果发现,RIF - 1和EMT6肿瘤的预处理乳酸水平和预处理乳酸脱氢酶(LDH)活性相似,这表明稳态乳酸水平不太可能是预测放射治疗反应的可靠指标。在10 Gy伽马射线照射后,EMT6肿瘤在48小时时相对于预处理乳酸水平下降了21%(从1.04±0.22降至0.82±0.16;P = 0.06);在20 Gy照射后,48小时时观察到下降了40%(从1.34±0.27降至0.81±0.10;P = 0.07)。与之前在RIF - 1肿瘤中检测到的变化相反,在对照EMT6肿瘤或接受4 Gy伽马射线治疗的肿瘤中未观察到乳酸水平有显著变化,RIF - 1肿瘤在2 Gy和4 Gy照射后48小时时乳酸均显著下降。与RIF - 1肿瘤相比,EMT6肿瘤中放射对乳酸水平的降低作用较小,这可能归因于EMT6肿瘤较高的缺氧比例和较低的放射敏感性(《国际放射肿瘤学、生物学与物理学杂志》10卷,695 - 712页,1984年)。然而,乳酸水平的下降并未严格反映对20 Gy高剂量治疗的反应程度。这项研究与我们早期的研究(《国际放射肿瘤学、生物学与物理学杂志》36卷,635 - 639页,1996年)共同提供了证据,支持稳态肿瘤乳酸水平的变化可能作为肿瘤对2至4 Gy量级伽马射线反应的敏感早期指标这一假设。

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