Water is an essential component of many biochemical reactions. Deuterated water (D₂O) has been used to study cell kinetics, protein synthesis, and metabolism. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with deuterium due to high metabolic activity, thus allowing imaging of biosynthetically labeled metabolites within tumors in vivo. We initiated systemic D₂O labeling in two established tumor xenograft models, HT-29 and MiaPaCa-2 and imaged mice by deuterium magnetic resonance spectroscopic imaging (dMRSI). After 14 days of tumor growth and 7 days of in vivo labeling, a clear contrast was demonstrated between the xenograft and the contralateral control limb in both models. The origin of the contrast was traced to an aliphatic peak at 1.8 ppm, which was identified by ex vivo NMR analysis to originate from cholesterol and cholesterol esters. Cholesterol is important for tumor cell proliferation, signaling, and malignant transformation, while current methods to monitor cholesterol synthesis and accumulation are limited. This deuterated water labeling-imaging approach could complement current cancer imaging techniques, allowing not only imaging of uptake but also synthesis of cholesterol to elucidate effects on tumor cholesterol metabolism in vivo.

中文翻译：

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体内氘水标记可通过氘核磁共振光谱对胆固醇进行肿瘤可视化

水是许多生化反应的重要组成部分。氘水（D ₂ O）已用于研究细胞动力学，蛋白质合成和代谢。我们假设由于高的代谢活性，迅速增殖的癌细胞将优先被氘标记，从而使体内肿瘤内生物合成标记的代谢物成像成为可能。我们在两个已建立的肿瘤异种移植模型HT-29和MiaPaCa-2中启动了系统性D ₂ O标记，并通过氘核磁共振波谱成像（dMRSI）对小鼠进行了成像。肿瘤生长14天和体内7天后标记后，两种模型的异种移植物和对侧对照肢体之间显示出明显的对比。造影剂的起源可追溯到脂肪族峰（1.8 ppm），该峰通过离体NMR分析确定为源自胆固醇和胆固醇酯。胆固醇对于肿瘤细胞的增殖，信号传导和恶性转化很重要，而目前监测胆固醇合成和积累的方法受到限制。这种氘化水标记成像方法可以补充当前的癌症成像技术，不仅可以对摄取成像，还可以合成胆固醇，以阐明对体内肿瘤胆固醇代谢的影响。