美国纪念斯隆-凯特琳肿瘤中心的Kayvan R. Keshari团队近日取得一项新成果。他们利用人类前列腺癌的超高极化MRI技术，发现乳酸水平随着单羧酸盐转运蛋白1驱动的肿瘤级别的增加而增加。2019年9月26日，国际知名学术期刊《细胞—代谢》在线发表了这一成果。

研究人员对患者的丙酮酸代谢进行了成像，评估了原发性前列腺癌情况下运输和转化的可重复性。研究人员表明，在接受两次单独注射的患者中或在整个患者中，丙酮酸达到最大量的时间没有显著变化。此外，研究人员表明乳酸随Gleason评级的增加而增加。RNA测序数据表明，主要的丙酮酸摄取转运蛋白（单羧酸盐转运蛋白1）显著增加。在高乳酸信号区域还观察到蛋白质表达增加，暗示它是体内乳酸信号的驱动者。针对功能性突变的靶向DNA测序显示，PTEN缺失患者出现的乳酸最高。这项工作确定了功能性基因组改变与超高极化丙酮酸MRI代谢信息之间的潜在联系。

据了解，使用超高极化磁共振的代谢成像可以提高MRI的灵敏度，尽管它尚无法提供人体内生物化学的相关变化。

附：英文原文

Title: Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1

Author: Kristin L. Granlund, Sui-Seng Tee, Hebert A. Vargas, Serge K. Lyashchenko, Ed Reznik, Samson Fine, Vincent Laudone, James A. Eastham, Karim A. Touijer, Victor E. Reuter, Mithat Gonen, Ramon E. Sosa, Duane Nicholson, YanWei W. Guo, Albert P. Chen, James Tropp, Fraser Robb, Hedvig Hricak, Kayvan R. Keshari

Issue&Volume: 26 September 2019

Abstract: 

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.

DOI: 10.1016/j.cmet.2019.08.024

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30498-X