NMR visibility of deuterium‐labeled liver glycogen in vivo

Abstract

Deuterium metabolic imaging (DMI) combined with [6,6'-2 H 2 ]-glucose has the potential to detect glycogen synthesis in the liver. However, the similar chemical shifts of [6,6'-2 H 2 ]-glucose and [6,6'-2 H 2 ]-glycogen in the 2 H NMR spectrum make unambiguous detection and separation difficult in vivo, in contrast to comparable approaches using 13 C MRS. Here the NMR visibility of 2 H-labeled glycogen is investigated to better understand its potential contribution to the observed signal in liver following administration of [6,6'-2 H 2 ]-glucose. Methods: Mice were provided drinking water containing 2 H-labeled glucose. Highresolution NMR analyses was performed of isolated liver glycogen in solution, before and after the addition of the glucose-releasing enzyme amyloglucosidase. Results: 2 H-labeled glycogen was barely detectable in solution using 2 H NMR because of the very short T 2 (<2 ms) of 2 H-labeled glycogen, giving a spectral line width that is more than five times as broad as that of 13 C-labeled glycogen (T 2 = ~10 ms). Conclusion: 2 H-labeled glycogen is not detectable with 2 H MRS(I) under in vivo conditions, leaving 13 C MRS as the preferred technique for in vivo detection of glycogen.

Deuterium Metabolic Imaging—Rediscovery of a Spectroscopic Tool

“…The 2 H spectrum of biologically relevant enriched metabolites is somewhat compressed (similar to 1 H-MRS), which might create difficulty in separating the different resonances. An example of that is the unsuccessful attempt made by Feyter et al to resolve D-[6,6′- 2 H 2 ] glucose from glycogen in the 2 H spectrum due to overlap of these resonances [ 74 ]. The contribution of natural abundance HDO (about 10 mM) represents a potential concern if the intent is to detect 2 H substrates or metabolites with similar chemical shifts (around 4.7 ppm).…”

“…Moreover, they showed the storage of [6,6′- 2 H 2 ] glucose as glycogen in the liver of both rats and humans [ 1 ]. However, a more recent attempt to visualize liver glycogen storage by providing mice with [6,6′- 2 H 2 ] glucose in drinking water did not achieve the desired 2 H-labeled glycogen signal due to a very short T 2 (<2 ms) [ 74 ]. Kreis et al [ 3 ] took the use of D-[6,6′- 2 H 2 ] glucose even further and presented a method to quantitate the tumor glucose flux while using 3D accelerated chemical shift images of the tumor before and after chemotherapy in a murine lymphoma model.…”

Deuterium MRSI characterizations of glucose metabolism in orthotopic pancreatic cancer mouse models

“…MR spectroscopy (MRS) and spectroscopic imaging (MRSI), following the administration of deuterated metabolites, have recently been introduced and applied to image tissue metabolism 25–34 . Exogenously administered 2 H 6,6′ ‐glucose was found to originate 2 H 4,4′ ‐glutamate and 2 H 4,4′ ‐glutamine peaks in healthy brains, as well as a 2 H 3,3′ ‐lactate signature in tumors; a significant production of 2 H‐water was also detected in all the tissues.…”

Non-invasive Analysis of Human Liver Metabolism by Magnetic Resonance Spectroscopy

“…In addition, 2 H T1 values are much shorter compared to those of 1 H, 13 C, or 31 P allowing more free-induction decays to be collected per unit time thereby effectively boosting sensitivity. However, for large molecular weight metabolites such as glycogen that exhibit very short spin-spin (T2) relaxation times, MR visibility of the 2 H label may be severly compromised [60]. Since the coupling constants of 2 H with neighboring 1 H nuclei are relatively small, 2 H signals are not substantially degraded by these interactions and can therefore be observed in the absence of broadband 1 H decoupling.…”