Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas.

Abstract

PURPOSE:

Prognostically favorable IDH-mutant gliomas are known to produce oncometabolite D-2-hydroxyglutarate (2HG). In this study, we investigated metabolite-based features of patients with grade 2 and 3 glioma using 2HG-specific in vivo MR spectroscopy, to determine their relationship with image-guided tissue pathology and predictive role in progression-free survival (PFS).

METHODS:

Forty-five patients received pre-operative MRIs that included 3-D spectroscopy optimized for 2HG detection. Spectral data were reconstructed and quantified to compare metabolite levels according to molecular pathology (IDH1R132H, 1p/19q, and p53); glioma grade; histological subtype; and T2 lesion versus normal-appearing white matter (NAWM) ROIs. Levels of 2HG were correlated with other metabolites and pathological parameters (cellularity, MIB-1) from image-guided tissue samples using Pearson's correlation test. Metabolites predictive of PFS were evaluated with Cox proportional hazards models.

RESULTS:

Quantifiable levels of 2HG in 39/42 (93%) IDH+ and 1/3 (33%) IDH- patients indicated a 91.1% apparent detection accuracy. Myo-inositol/total choline (tCho) showed reduced values in astrocytic (1p/19q-wildtype), p53-mutant, and grade 3 (vs. 2) IDH-mutant gliomas (p < 0.05), all of which exhibited higher proportions of astrocytomas. Compared to NAWM, T2 lesions displayed elevated 2HG+ γ-aminobutyric acid (GABA)/total creatine (tCr) (p < 0.001); reduced glutamate/tCr (p < 0.001); increased myo-inositol/tCr (p < 0.001); and higher tCho/tCr (p < 0.001). Levels of 2HG at sampled tissue locations were significantly associated with tCho (R = 0.62; p = 0.002), total NAA (R = - 0.61; p = 0.002) and cellularity (R = 0.37; p = 0.04) but not MIB-1. Increasing levels of 2HG/tCr (p = 0.0007, HR 5.594) and thresholding (≥ 0.905, median value; p = 0.02) predicted adverse PFS.

CONCLUSION:

In vivo 2HG detection can reasonably be achieved on clinical scanners and increased levels may signal adverse PFS.

• Authors: Adam W Autry, Marisa Lafontaine, Llewellyn Jalbert, Elizabeth Phillips, Joanna J Phillips, Javier Villanueva-Meyer, Mitchel S Berger, Susan M Chang, Yan Li
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 159 Issue 1 Pg. 43-52 (Aug 2022) ISSN: 1573-7373 [Electronic] United States
• PMID: 35672531 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Glutarates
• Receptors, Antigen, T-Cell
• Tumor Suppressor Protein p53
• alpha-hydroxyglutarate
• Inositol
• Isocitrate Dehydrogenase

Topics

• Brain Neoplasms (diagnostic imaging, genetics, surgery)
• Glioma (diagnostic imaging, genetics, surgery)
• Glutarates
• Humans
• Inositol
• Isocitrate Dehydrogenase (genetics, metabolism)
• Magnetic Resonance Spectroscopy (methods)
• Mutation
• Receptors, Antigen, T-Cell (metabolism)
• Tumor Suppressor Protein p53