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Biomolecular NMR


Development of Hyperpolarized Metabolic Contrast Agents Using PASADENA (Application Note 21)

Eduard Y. Chekmenev, et al.
California Institute of Technology, Pasadena, CA

  • Development of Hyperpolarized Metabolic Contrast Agents Using PASADENA (Application Note 21)
  • Testimonial from Thomas C. Glenn, PhD

Dissolution DNP

DNP is now a well-established technique that is facilitated by the transfer of the polarization of unpaired electrons to the nuclei under study. Dissolution DNP methods require the sample be kept cold (e.g., <4 K) while irradiated by microwaves in a strong magnetic field (e.g., 3 T). After irradiation, the sample is rapidly dissolved using hot pressurized solvent and transferred to an NMR tube or an injection syringe for immediate NMR or MRI data acquisition. A free-radical doping agent must be present in the sample at mM concentrations during microwave irradiation in order to provide the needed nuclear polarization for intermolecular transfer. Generally, acceptable levels of polarization are achieved using irradiation times that are several tens of minutes to several hours in length.

Low-temperature DNP, a method pioneered by the laboratory of Robert Griffin, however, is a slightly different technique than dissolution DNP. Both hyperpolarization and NMR acquisition take place in the solid state, where the hyperpolarized signal is effectively continually regenerated which allows for data acquisition from hours to many days.


Parahydrogen-Induced Polarization (PHIP)

PHIP is a fairly well-established technique that transfers polarization directly from parahydrogen (para-H2) to nearby nuclei of interest or by using RF-based magnetization transfer methods. For organic molecules, para-H2 is either added directly across unsaturated carbon bonds or mixed with the sample under conditions such that polarization can transfer from para-H2 to sites within the molecule. Some advantages of PHIP over DNP are that a polarized sample may be attained quite quickly (on the order of seconds or minutes) and that free-radical doping agents are not required.


Metabolic Imaging
Perhaps the most exciting consequence of signal enhancement obtained using DNP and PHIP is the potential for in vivo 1H, 13C and 15N monitoring of metabolism. In particular, 13C MRI imaging using hyperpolarized 13C-enriched organic molecules offers significant advantages over 1H-based imaging techniques, because background signals are not detected and the large chemical shift range for 13C leads to increased molecular selectivity. Currently there is interest in the use of isotopically enriched hyperpolarized substrates for medical imaging because detailed, metabolic information (substrate localization and biochemical transformations) and physiological information (e.g., intracellular pH) may be obtained. Although the signal enhancement of hyperpolarized spin one-half nuclei decays with T1, research is under way to establish long-lived nuclear states with the promise that metabolism may be studied over time scales of minutes, or even hours, instead of seconds.




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Kevin Millis, PhD

Kevin Millis, PhD

Senior Scientist, Application Development Manager

Kevin Millis, PhD, is the Senior Scientist and Market Development Manager for all NMR and mass spectrometry product lines. Kevin is responsible for Technical Services both internally and externally for all CIL customers as well as being responsible for the application and market development for the CIL products.


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