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

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

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

机译：人前列腺癌的超极化MRI揭示了由单羧酸盐转运蛋白转运蛋白的肿瘤等级增加的乳酸乳液

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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.

机译：使用超极化磁共振的代谢成像可以提高MRI的敏感性，尽管它提供了通知人类生物化学的相关变化的能力仍不清楚。在这项工作中，我们在患者中造成丙酮酸代谢，评估在原发性前列腺癌中的交付和转化的再现性。我们表明，在接受两种单独的注射或患者的患者中，丙酮酸的最大的时间不会显着变化。此外，我们表明乳酸乳酸率随着Gleason等级的增加。 RNA测序数据表明主要丙酮酸含量摄取转运蛋白，单羧酸盐转运蛋白。在高乳酸信号的区域中也观察到增加的蛋白质表达，这意味着它作为体内乳酸乳酸信号的驱动器。可操作性突变的靶向DNA测序显示PTEN损失患者发生的最高乳酸。这项工作识别可动作基因组改变与源自超极化丙酮酸MRI的代谢信息之间的潜在联系。

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《Cell metabolism》 |2020年第1期|共13页
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Granlund Kristin L.; Tee Sui-Seng; Vargas Hebert A.; Lyashchenko Serge K.; Reznik Ed; Fine Samson; Laudone Vincent; Eastham James A.; Touijer Karim A.; Reuter Victor E.; Gonen Mithat; Sosa Ramon E.; Nicholson Duane; Guo YanWei W.; Chen Albert P.; Tropp James; Robb Fraser; Hricak Hedvig; Keshari Kayvan R.;
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Mem Sloan Kettering Canc Ctr Radiol 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Radiol 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Radiol 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Radiochem &

Mol Imaging Probes RIMP Core 1275 York Ave New York NY;

Mem Sloan Kettering Canc Ctr Epidemiol &

Biostat 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Pathol 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Surg 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Surg 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Surg 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Pathol 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Epidemiol &

Biostat 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Radiol 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Radiol 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Radiol 1275 York Ave New York NY 10021 USA;

GE Healthcare Toronto ON Canada;

Berkshire Magnet Berkeley CA USA;

GE Healthcare Aurora OH USA;

Mem Sloan Kettering Canc Ctr Radiol 1275 York Ave New York NY 10021 USA;

Mem Sloan Kettering Canc Ctr Radiol 1275 York Ave New York NY 10021 USA;

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中图分类内分泌腺疾病及代谢病;
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1. Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1 [J] . Granlund Kristin L., Tee Sui-Seng, Vargas Hebert A., Cell metabolism . 2020,第1期

机译：人前列腺癌的超极化MRI揭示了由单羧酸盐转运蛋白转运蛋白的肿瘤等级增加的乳酸乳液
2. Metabolic reprogramming and validation of hyperpolarized 13C lactate as a prostate cancer biomarker using a human prostate tissue slice culture bioreactor [J] . KeshariK.R., SriramR., VanCriekingeM., The Prostate . 2013,第11期

机译：使用人类前列腺组织切片培养生物反应器对超极化的13C乳酸作为前列腺癌生物标志物进行代谢重编程和验证
3. Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. [J] . Albers MJ, Bok R, Chen AP, Cancer research: The official organ of the American Association for Cancer Research, Inc . 2008,第20期

机译：超极化的13C乳酸，丙酮酸和丙氨酸：用于前列腺癌检测和分级的非侵入性生物标志物。
4. A combination of intra- and peri-tumoral deep features from prostate bi-parametric MRI can distinguish clinically significant and insignificant prostate cancer [C] . Amogh Hiremath, Rakesh Shiradkar, Nathaniel Braman, Medical Imaging Conference . 2020

机译：前列腺双参数MRI的肿瘤内和肿瘤周围深部特征的组合可以区分临床上显着和不重要的前列腺癌
5. Monocarboxylate Transporter 1 modulates cancer cell pyruvate export and tumor growth [D] . Hong, Candice Sun 2016

机译：单羧酸盐转运蛋白1调节癌细胞丙酮酸的输出和肿瘤的生长
6. Elevated Tumor Lactate and Efflux in High-grade Prostate Cancer demonstrated by Hyperpolarized 13C Magnetic Resonance Spectroscopy of Prostate Tissue Slice Cultures [O] . Renuka Sriram, Mark Van Criekinge, Justin DeLos Santos, 2020

机译：前列腺组织切片培养物的超极化13C磁共振波谱显示高级前列腺癌中的肿瘤乳酸和外排量
7. Elevated Tumor Lactate and Efflux in High-grade Prostate Cancer demonstrated by Hyperpolarized 13C Magnetic Resonance Spectroscopy of Prostate Tissue Slice Cultures [O] . Renuka Sriram, Mark Van Criekinge, Justin DeLos Santos, 2020

机译：通过前列腺组织切片培养的超极化13C磁共振光谱证明了高级前列腺癌中升高的肿瘤乳酸和渗透

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

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