NMR visibility of deuterium-labeled liver glycogen in vivo

Abstract

Purpose: Deuterium metabolic imaging (DMI) combined with [6,6'-² H₂ ]-glucose has the potential to detect glycogen synthesis in the liver. However, the similar chemical shifts of [6,6'-² H₂ ]-glucose and [6,6'-² H₂ ]-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 H₂ ]-glucose.

Methods: Mice were provided drinking water containing ² H-labeled glucose. High-resolution 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 T₂ (<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 (T₂ = ~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.

Keywords: DMI; deuterium; glycogen.