Study of real time 13C metabolic fluxes using Dynamic Nuclear Polarization and Magnetic Resonance Spectroscopy

Commonly used acronym: DNP

Scope of the method

Alternative method relates to
  • Animal health
Alternative method is situated in
  • Basic Research
  • Translational - Applied Research
Type of alternative method
  • Other
In vitro and in vivo method
This method makes use of
  • Animal derived cells / tissues / organs

Description

Method keywords
  • hyperpolarization
  • 13C metabolic fluxes
  • 13C-MRS
  • in vitro and in vivo tool
Scientific area keywords
  • tumor metabolism
  • cardiac function
  • metabolic disorders
  • 13C metabolism
Method description

Hyper Polarized (HP) MR allows to considerably increase the sensitivity (>10.000) of MR spectroscopy and spectroscopic imaging. The hyperpolarized molecule can be injected at room temperature to a cell system or an in vivo model and its metabolism can be followed over a few minutes.The technique has been used in vivo or in vitro to assess changes in metabolic fluxes through glycolysis, citric acid cycle, and fatty acid synthesis. HP MR studies using 13C pyruvate showed an increase in signal to noise ratio of more than 50.000 of the substrate and its metabolites (lactate and alanine), allowing for unique dynamic mapping of metabolism using spectroscopic imaging.

Lab equipment

The oxford instruments HyperSense DNP system is combined with our 11.7T preclinical Magnetic Resonance system (Bruker Biospin) for in vivo application or with our Bruker Ascend 600MHz NMR system for in vitro application. The Hypersense allows hyperpolarization of 13C-enriched substrates, direct dissolution and cooling down of the substrates and allows consecutive injection in the vascular system of the animal under study or in cell media for intro application.

Method status
  • Published in peer reviewed journal

Pros, cons & Future potential

Advantages

The method allows the assessment of real-time metabolic conversion (i.e. of 13C-pyruvate into 13C-lactate) with high sensitivity and non-invasively (while used in vivo). It constitutes a key tool to address fundamental questions in the scope of metabolism in several fields, including oncology, cardiology, metabolic disorders, etc...

Challenges

A major limitation of DNP is a requirement of a long relaxation time T1 for the 13C enriched substrate. The useful monitoring time is limited to 5X T1, which includes dissolution, injection, and imaging. Hence, for pyruvate, there is a maximum of 3 min of useful measuring time. Nevertheless, the technique has already shown numerous applications for detecting treatment response in animals.

Modifications

No modifications are planned in the near future.

Future & Other applications
  • Metabolic disorders,
  • Cardiac function metabolism,
  • Cancer metabolism.

References, associated documents and other information

References

Magnetic resonance imaging of cancer metabolism with hyperpolarized 13C-labeled cell metabolites. Hesketh RL, Brindle KM. Curr Opin Chem Biol. 2018 Aug;45:187-194. doi: 10.1016/j.cbpa.2018.03.004. Epub 2018 Jul 13.

Monitoring chemotherapeutic response by hyperpolarized 13C-fumarate MRS and diffusion MRI. Mignion L, Dutta P, Martinez GV, Foroutan P, Gillies RJ, Jordan BF. Cancer Res. 2014 Feb 1;74(3):686-94. doi: 10.1158/0008-5472.CAN-13-1914.

Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects. Corbet C, Bastien E, Draoui N, Doix B, Mignion L, Jordan BF, Marchand A, Vanherck JC, Chaltin P, Schakman O, Becker HM, Riant O, Feron O. Nat Commun. 2018 Mar 23;9(1):1208. doi: 10.1038/s41467-018-03525-0

Associated documents

Contact person

Bénédicte Jordan

Organisations

UCLouvain
Louvain Drug Research Institute, Nuclear and Electron Spin Technologies platform (NEST)
Belgium