Molecular imaging of tumor metabolism: Insight from pyruvate- and glucose-based deuterium MRI studies

被引:13
作者
Montrazi, Elton T. [1 ]
Sasson, Keren [2 ]
Agemy, Lilach [2 ]
Scherz, Avigdor [2 ]
Frydman, Lucio [1 ]
机构
[1] Weizmann Inst Sci, Dept Chem & Biol Phys, Rehovot, Israel
[2] Weizmann Inst Sci, Dept Plant & Environm Sci, Rehovot, Israel
基金
以色列科学基金会;
关键词
IN-VIVO; PANCREATIC-CANCER;
D O I
10.1126/sciadv.adm8600
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cancer diagnosis by metabolic MRI proposes to follow the fate of glycolytic precursors such as pyruvate or glucose, and their in vivo conversion into lactate. This study compares the H-2 MRI outlooks afforded by these metabolites when targeting a pancreatic cancer model. Exogenously injected [3,3',3 ''-H-2(3)]-pyruvate was visible only briefly; it generated a deuterated lactate signal throughout the body that faded after similar to 5 min, showing a minor concentration bias at the rims of the tumors. [6,6 '-H-2(2)]-glucose by contrast originated a lactate signal that localized clearly within the tumors, persisting for over an hour. Investigations alternating deuterated and nondeuterated glucose injections revealed correlations between the lactate generation and the glucose available at the tumor, evidencing a continuous and avid glucose consumption generating well-localized lactate signatures as driven by the Warburg effect. This is by contrast to the transient and more promiscuous pyruvate-to-lactate transformation, which seemed subject to transporter and kinetics effects. The consequences of these observations within metabolic MRI are briefly discussed.
引用
收藏
页数:9
相关论文
共 39 条
[31]   Hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion is rate-limited by monocarboxylate transporter-1 in the plasma membrane [J].
Rao, Yi ;
Gammon, Seth ;
Zacharias, Niki M. ;
Liu, Tracy ;
Salzillo, Travis ;
Xi, Yuanxin ;
Wang, Jing ;
Bhattacharya, Pratip ;
Piwnica-Worms, David .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (36) :22378-22389
[32]   Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose [J].
Rodrigues, Tiago B. ;
Serrao, Eva M. ;
Kennedy, Brett W. C. ;
Hu, De-En ;
Kettunen, Mikko I. ;
Brindle, Kevin M. .
NATURE MEDICINE, 2014, 20 (01) :93-+
[33]   MRI with hyperpolarised [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model [J].
Serrao, Eva M. ;
Kettunen, Mikko I. ;
Rodrigues, Tiago B. ;
Dzien, Piotr ;
Wright, Alan J. ;
Gopinathan, Aarthi ;
Gallagher, Ferdia A. ;
Lewis, David Y. ;
Frese, Kristopher K. ;
Almeida, Jaime ;
Howat, William J. ;
Tuveson, David A. ;
Brindle, Kevin M. .
GUT, 2016, 65 (03) :465-475
[34]   Pilot Study Experiences With Hyperpolarized [1-13C]pyruvate MRI in Pancreatic Cancer Patients [J].
Stodkilde-Jorgensen, Hans ;
Laustsen, Christoffer ;
Hansen, Esben Sovso Szocska ;
Schulte, Rolf ;
Ardenkjaer-Larsen, Jan Henrik ;
Comment, Arnaud ;
Frokiaer, Jorgen ;
Ringgaard, Steffen ;
Bertelsen, Lotte Bonde ;
Ladekarl, Morten ;
Weber, Britta .
JOURNAL OF MAGNETIC RESONANCE IMAGING, 2020, 51 (03) :961-963
[35]   Comprehensive Literature Review of Hyperpolarized Carbon-13 MRI: The Road to Clinical Application [J].
Vaeggemose, Michael ;
Schulte, Rolf F. ;
Laustsen, Christoffer .
METABOLITES, 2021, 11 (04)
[36]  
Wallis C., 2018, Why pancreatic cancer is on the rise, P24
[37]   Hyperpolarized 13C MRI: State of the Art and Future Directions [J].
Wang, Zhen J. ;
Ohliger, Michael A. ;
Larson, Peder E. Z. ;
Gordon, Jeremy W. ;
Bok, Robert A. ;
Slater, James ;
Villanueva-Meyer, Javier E. ;
Hess, Christopher P. ;
Kurhanewicz, John ;
Vigneron, Daniel B. .
RADIOLOGY, 2019, 291 (02) :273-284
[38]   ORIGIN OF CANCER CELLS [J].
WARBURG, O .
SCIENCE, 1956, 123 (3191) :309-314
[39]   The metabolism of tumors in the body. [J].
Warburg, O ;
Wind, F ;
Negelein, E .
JOURNAL OF GENERAL PHYSIOLOGY, 1927, 8 (06) :519-530