Data from Deuterium Metabolic Imaging Differentiates Glioblastoma Metabolic Subtypes and Detects Early Response to Chemoradiotherapy
- Abstract:
- <div>Abstract<p>Metabolic subtypes of glioblastoma (GBM) have different prognoses and responses to treatment. Deuterium metabolic imaging with <sup>2</sup>H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. In this study, we used <sup>2</sup>H magnetic resonance spectroscopy and magnetic resonance spectroscopic imaging (MRSI) measurements of [6,6′-<sup>2</sup>H<sub>2</sub>]glucose metabolism to identify metabolic subtypes and their responses to chemoradiotherapy in patient-derived GBM xenografts <i>in vivo</i>. The metabolism of patient-derived cells was first characterized <i>in vitro</i> by measuring the oxygen consumption rate, a marker of mitochondrial tricarboxylic acid cycle activity, as well as the extracellular acidification rate and <sup>2</sup>H-labeled lactate production from [6,6′-<sup>2</sup>H<sub>2</sub>]glucose, which are markers of glycolytic activity. Two cell lines representative of a glycolytic subtype and two representative of a mitochondrial subtype were identified. <sup>2</sup>H magnetic resonance spectroscopy and MRSI measurements showed similar concentrations of <sup>2</sup>H-labeled glucose from [6,6′-<sup>2</sup>H<sub>2</sub>]glucose in all four tumor models when implanted orthotopically in mice. The glycolytic subtypes showed higher concentrations of <sup>2</sup>H-labeled lactate than the mitochondrial subtypes and normal-appearing brain tissue, whereas the mitochondrial subtypes showed more glutamate/glutamine labeling, a surrogate for tricarboxylic acid cycle activity, than the glycolytic subtypes and normal-appearing brain tissue. The response of the tumors to chemoradiation could be detected within 24 hours of treatment completion, with the mitochondrial subtypes showing a decrease in both <sup>2</sup>H-labeled glutamate/glutamine and lactate concentrations and glycolytic tumors showing a decrease in <sup>2</sup>H-labeled lactate concentration. This technique has the potential to be used clinically for treatment selection and early detection of treatment response.</p>Significance:<p>Deuterium magnetic resonance spectroscopic imaging of glucose metabolism has the potential to differentiate between glycolytic and mitochondrial metabolic subtypes in glioblastoma and to evaluate early treatment responses, which could guide patient treatment.</p></div>
- Authors:
- JCM Low, J Cao, F Hesse, AJ Wright, A Tsyben, I Alshamleh, R Mair, KM Brindle
- Publication date:
- 14th Jun 2024
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- DOI