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Deuterium MRS of early treatment-induced changes in tumour lactate in vitro
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2021-08-18 , DOI: 10.1002/nbm.4599 Josephine L Tan 1, 2 , Daniel Djayakarsana 1, 2 , Hanzhi Wang 1, 2 , Rachel W Chan 2 , Colleen Bailey 1, 2, 3 , Angus Z Lau 1, 2
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2021-08-18 , DOI: 10.1002/nbm.4599 Josephine L Tan 1, 2 , Daniel Djayakarsana 1, 2 , Hanzhi Wang 1, 2 , Rachel W Chan 2 , Colleen Bailey 1, 2, 3 , Angus Z Lau 1, 2
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Elevated production of lactate is a key characteristic of aberrant tumour cell metabolism and can be non-invasively measured as an early marker of tumour response using deuterium (2H) MRS. Following treatment, changes in the 2H-labelled lactate signal could identify tumour cell death or impaired metabolic function, which precede morphological changes conventionally used to assess tumour response. In this work, the association between apoptotic cell death, extracellular lactate concentration, and early treatment-induced changes in the 2H-labelled lactate signal was established in an in vitro tumour model. Experiments were conducted at 7 T on acute myeloid leukaemia (AML) cells, which had been treated with 10 μg/mL of the chemotherapeutic agent cisplatin. At 24 and 48 h after cisplatin treatment the cells were supplied with 20 mM of [6,6′-2H2]glucose and scanned over 2 h using a two-dimensional 2H MR spectroscopic imaging sequence. The resulting signals from 2H-labelled glucose, lactate, and water were quantified using a spectral fitting algorithm implemented on the Oxford Spectroscopy Analysis MATLAB toolbox. After scanning, the cells were processed for histological stains (terminal deoxynucleotidyl transferase UTP nick end labelling and haematoxylin and eosin) to assess apoptotic area fraction and cell morphology respectively, while a colorimetric assay was used to measure extracellular lactate concentrations in the supernatant. Significantly lower levels of 2H-labelled lactate were observed in the 48 h treated cells compared with the untreated and 24 h treated cells, and these changes were significantly correlated with an increase in apoptotic fraction and a decrease in extracellular lactate. By establishing the biological processes associated with treatment-induced changes in the 2H-labelled lactate signal, these findings suggest that 2H MRS of lactate may be valuable in evaluating early tumour response.
中文翻译：
早期治疗诱导的体外肿瘤乳酸变化的氘 MRS
乳酸产生升高是异常肿瘤细胞代谢的一个关键特征，并且可以使用氘 ( 2 H) MRS作为肿瘤反应的早期标志物进行非侵入性测量。治疗后，2 H标记的乳酸信号的变化可以识别肿瘤细胞死亡或代谢功能受损，这在通常用于评估肿瘤反应的形态学变化之前。在这项工作中，凋亡细胞死亡、细胞外乳酸浓度和早期治疗引起的2在体外肿瘤模型中建立了 H标记的乳酸信号。在 7 T 下对已用 10 μg/mL 化疗剂顺铂处理的急性髓性白血病 (AML) 细胞进行实验。在顺铂处理后 24 和 48 小时，向细胞提供 20 mM [6,6'- 2 H 2 ]葡萄糖，并使用二维2 H MR 光谱成像序列扫描 2 小时。来自2的结果信号使用在牛津光谱分析 MATLAB 工具箱上实施的光谱拟合算法对 H 标记的葡萄糖、乳酸和水进行量化。扫描后，对细胞进行组织学染色（末端脱氧核苷酸转移酶 UTP 缺口末端标记和苏木精和伊红）以分别评估凋亡区域分数和细胞形态，同时使用比色法测量上清液中的细胞外乳酸浓度。2的水平显着降低与未处理和 24 小时处理的细胞相比，在处理 48 小时的细胞中观察到 H标记的乳酸，这些变化与凋亡分数的增加和细胞外乳酸的减少显着相关。通过建立与治疗诱导的2 H标记的乳酸信号变化相关的生物学过程，这些发现表明乳酸的2 H MRS 在评估早期肿瘤反应方面可能很有价值。
更新日期：2021-08-18
中文翻译：
早期治疗诱导的体外肿瘤乳酸变化的氘 MRS
乳酸产生升高是异常肿瘤细胞代谢的一个关键特征，并且可以使用氘 ( 2 H) MRS作为肿瘤反应的早期标志物进行非侵入性测量。治疗后，2 H标记的乳酸信号的变化可以识别肿瘤细胞死亡或代谢功能受损，这在通常用于评估肿瘤反应的形态学变化之前。在这项工作中，凋亡细胞死亡、细胞外乳酸浓度和早期治疗引起的2在体外肿瘤模型中建立了 H标记的乳酸信号。在 7 T 下对已用 10 μg/mL 化疗剂顺铂处理的急性髓性白血病 (AML) 细胞进行实验。在顺铂处理后 24 和 48 小时，向细胞提供 20 mM [6,6'- 2 H 2 ]葡萄糖，并使用二维2 H MR 光谱成像序列扫描 2 小时。来自2的结果信号使用在牛津光谱分析 MATLAB 工具箱上实施的光谱拟合算法对 H 标记的葡萄糖、乳酸和水进行量化。扫描后，对细胞进行组织学染色（末端脱氧核苷酸转移酶 UTP 缺口末端标记和苏木精和伊红）以分别评估凋亡区域分数和细胞形态，同时使用比色法测量上清液中的细胞外乳酸浓度。2的水平显着降低与未处理和 24 小时处理的细胞相比，在处理 48 小时的细胞中观察到 H标记的乳酸，这些变化与凋亡分数的增加和细胞外乳酸的减少显着相关。通过建立与治疗诱导的2 H标记的乳酸信号变化相关的生物学过程，这些发现表明乳酸的2 H MRS 在评估早期肿瘤反应方面可能很有价值。
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