¹H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors.
Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used (1) H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A TE =19 ms PRESS sequence at 9.4 T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N-acetylaspartate, aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain.
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Keith M
KM
Hulsey
Tomoyuki
T
Mashimo
Abhishek
A
Banerjee
Todd C
TC
Soesbe
Jeffrey S
JS
Spence
Vamsidhara
V
Vemireddy
Elizabeth A
EA
Maher
Robert M
RM
Bachoo
Changho
C
Choi
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D004195:Disease Models, Animal; D059330:GABAergic Neurons / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D055442:Metabolome; D051379:Mice; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*
D005973:Glutamine
1H MRS; 9.4 T; GBM; PRESS; human orthotopic tumor (HOT) mouse model; neurochemical profile