title: High-resolution magic angle spinning magnetic resonance spectroscopy detects glycine as a biomarker in brain tumors.
abstract: The non-essential amino acid neurotransmitter glycine (Gly) may serve as a biomarker for brain tumors. Using 36 biopsies from patients with brain tumors [12 glioblastoma multiforme (GBM); 10 low-grade (LG), including 7 schwannoma and 3 pylocytic astrocytoma; 7 meningioma (MN); 7 brain metastases (MT), including 3 adenocarcinoma and 4 breast cancer] and 9 control biopsies from patients undergoing surgery for epilepsy, we tested the hypothesis that the presence of glycine may distinguish among these brain tumor types. Using high-resolution magic angle spinning (HRMAS) 1H magnetic resonance spectroscopy (MRS), we determined a theoretically optimum echo time (TE) of 50 ms for distinguishing Gly signals from overlapping myo-inositol (Myo) signals and tested our methodology in phantom and biopsy specimens. Quantitative analysis revealed higher levels of Gly in tumor biopsies (all combined) relative to controls; Gly levels were significantly elevated in LG, MT and GBM biopsies (P<or=0.05). Residual Myo levels were elevated in LG and MT and reduced in MN and GBM (P<0.05 vs. control levels). We observed higher levels of Gly in GBM as compared to LG tumors (P=0.05). Meanwhile, although Gly levels in GBM and MT did not differ significantly from each other, the Gly:Myo ratio did distinguish GBM from MT (P<0.003) and from all other groups, a distinction that has not been adequately made previously. We conclude from these findings that Gly can serve as a biomarker for brain tumors and that the Gly:Myo ratio may be a useful index for brain tumor classification.
authors.affiliation: NMR Surgical Laboratory, Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Righi
authors.forename: Ovidiu C
authors.initials: OC
authors.lastname: Andronesi
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Mintzopoulos
authors.forename: Peter M
authors.initials: PM
authors.lastname: Black
authors.forename: A Aria
authors.initials: AA
authors.lastname: Tzika
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D005998:Glycine / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000032:analysis / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007294:Inositol; D005998:Glycine