Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1
Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1
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DOI：
10.1016/j.cmet.2019.08.024
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发表时间：
2020-01-07
期刊：
影响因子：
29
通讯作者：
Keshari, Kayvan R.
中科院分区：
文献类型：
--
作者：
Granlund, Kristin L.;Tee, Sui-Seng;Keshari, Kayvan R.
使用超极化磁共振的代谢成像可以提高 MRI 的灵敏度，但其告知人类生物化学相关变化的能力仍不清楚。在这项工作中，我们对患者的丙酮酸代谢进行成像，评估原发性前列腺癌中递送和转化的可重复性。我们发现，在接受两次单独注射的患者或不同患者之间，丙酮酸达到最大浓度的时间没有显着差异。此外，我们表明乳酸随着格里森等级的增加而增加。 RNA 测序数据表明，主要的丙酮酸摄取转运蛋白、单羧酸转运蛋白 1 显着增加。在高乳酸信号区域也观察到蛋白质表达增加，表明它是体内乳酸信号的驱动因素。针对可操作突变的靶向 DNA 测序显示，PTEN 缺失患者的乳酸水平最高。这项工作确定了可操作的基因组改变和来自超极化丙酮酸 MRI 的代谢信息之间的潜在联系。
Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients. Furthermore, we show that lactate increases with Gleason grade. RNA sequencing data demonstrate a significant increase in the predominant pyruvate uptake transporter, monocarboxylate transporter 1. Increased protein expression was also observed in regions of high lactate signal, implicating it as the driver of lactate signal in vivo. Targeted DNA sequencing for actionable mutations revealed the highest lactate occurred in patients with PTEN loss. This work identifies a potential link between actionable genomic alterations and metabolic information derived from hyperpolarized pyruvate MRI.