Detecting treatment response in a model of human breast adenocarcinoma using hyperpolarised [1-13C]pyruvate and [1,4-13C2]fumarate.
Detecting treatment response in a model of human breast adenocarcinoma using hyperpolarised [1-13C]pyruvate and [1,4-13C2]fumarate.
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DOI：
10.1038/sj.bjc.6605945
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发表时间：
2010-10-26
影响因子：
8.8
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最近引入的动态核极化技术允许在静脉注射13c标记的细胞底物后对体内肿瘤细胞代谢进行无创成像。在阿霉素治疗后，对MDA-MB-231细胞和植入的MDA-MB-231肿瘤中超极化[1- 13c]丙酮酸和[1,4- 13c2]富马酸代谢的变化进行了评估。MDA-MB-231细胞处理诱导凋亡，并伴有[1-13C]丙酮酸和乳酸之间超极化13C标记通量的减少，这与细胞NAD(H)辅酶池的减少有关。富马酸转化为苹果酸的速率也有所增加，这伴随着细胞坏死的发生。在体内，在药物治疗后，丙酮酸和乳酸之间13C标签交换的减少以及富马酸和苹果酸之间通量的增加，显示在没有任何可检测到的肿瘤大小变化的情况下发生。我们在这里表明，人类乳腺腺癌肿瘤模型对药物治疗的早期反应可以通过施用超极化[1- 13c]丙酮酸和[1,4- 13c2]富马酸来进行。因此，这些技术可用于临床检测乳腺肿瘤对治疗的早期反应。
The recent introduction of a dynamic nuclear polarisation technique has permitted noninvasive imaging of tumour cell metabolism in vivo following intravenous administration of 13C-labelled cell substrates. Changes in hyperpolarised [1-13C]pyruvate and [1,4-13C2]fumarate metabolism were evaluated in both MDA-MB-231 cells and in implanted MDA-MB-231 tumours following doxorubicin treatment. Treatment of MDA-MB-231 cells resulted in the induction of apoptosis, which was accompanied by a decrease in hyperpolarised 13C label flux between [1-13C]pyruvate and lactate, which was correlated with a decrease in the cellular NAD(H) coenzyme pool. There was also an increase in the rate of fumarate conversion to malate, which accompanied the onset of cellular necrosis. In vivo, the decrease in 13C label exchange between pyruvate and lactate and the increased flux between fumarate and malate, following drug treatment, were shown to occur in the absence of any detectable change in tumour size. We show here that the early responses of a human breast adenocarcinoma tumour model to drug treatment can be followed by administration of both hyperpolarised [1-13C]pyruvate and [1,4-13C2]fumarate. These techniques could be used, therefore, in the clinic to detect the early responses of breast tumours to treatment.