Quantitative Hdo Production from Glucose-d7 for Monitoring Tumor Metabolism
Abstract
Purpose
This work seeks to extend the quantitative methods developed for glucose-d2 to HDO production from glucose-d7 as a potential avenue for improving of metabolic monitoring using deuterium MR.
Methods
The validity of NMR quantification was validated by testing against known glucose concentrations in a solvent of distilled water containing natural abundance HDO. Spectroscopy was performed on the samples using a 300MHz vertical-bore Bruker NMR and line-broadened by 55Hz to mimic in vivo spectroscopy. Spectral fitting using a single Lorentzian line shape for HDO and a measured line shape for glucose gave a series of amplitudes for the two metabolites which were corrected for the T1 weighting due to rapid TR. Finally, the natural abundance concentration of deuterium was fitted. The NMR validated quantification was applied to analyze dynamic spectroscopy of healthy and tumor-bearing mice following intravenous infusion of glucose-d7. DAOY medulloblastoma cells were implanted in the brains of tumor-bearing mice and allowed to grow until symptoms of tumor burden began to show. A single-turn surface coil for transmit and receive was used to localize 2H signal to the brain of the mice. The quantification described above was used in conjunction with a modified Kety-Tofts model to produce quantitative concentration time curves.
Results
Spectral fitting of the NMR data recovered the HDO and glucose concentrations with a linear fit R2 of 0.988. The fitted natural abundance concentration of HDO was 15.3mM corresponding to a natural abundance percentage of 0.0138%. Tumor-bearing models demonstrated more HDO production than healthy models. Cerebral concentrations of exogenous glucose reached maximum concentration of 5mM - 8mM, and the HDO concentration varied from natural abundance to greater than 40mM.
Conclusion
Quantitative HDO production from glucose-d7 is demonstrated to be a surrogate for tumor metabolism in this study.