Deuterium Metabolic Imaging Phenotypes Mouse Glioblastoma Heterogeneity Through Glucose Turnover Kinetics

• DOI: 10.1101/2024.06.23.600246
• Publication Date: 2024-06-29T17:30:17Z
• Authors: Rui V. Simões; Rafael N. Henriques; Jonas L Olesen; Beatriz M. Cardoso; Francisca F. Fern...; Mariana A.V. Mont...; Sune N Jespersen; Tânia Carvalho; Noam Shemesh
• Keywords: mitochondrial metabolism; QH301-705.5; Science; Q; glioblastoma; R; Medicine; deuterium metabolic imaging; glycolysis; Biology (General); kinetic modeling; mouse; cancer biology

Abstract Glioblastomas are aggressive brain tumors with dismal prognosis. One of the main bottlenecks for developing more effective therapies glioblastoma stems from their histologic and molecular heterogeneity, leading to distinct tumor microenvironments disease phenotypes. Effectively characterizing these features would improve clinical management glioblastoma. Glucose flux rates through glycolysis mitochondrial oxidation have been recently shown quantitatively depict proliferation in mouse models (GL261 CT2A tumors, 38±3 mm 3 ) using dynamic glucose-enhanced (DGE) deuterium spectroscopy. However, spatial microenvironment phenotypes remain hitherto unresolved. Here, we develop a DGE Deuterium Metabolic Imaging (DMI) approach profiling glucose conversion kinetics. Using multimodal combination models, novel strategies spectroscopic imaging noise attenuation, histopathological correlations, show that lactate turnover mirrors phenotype differences between GL261 (59±7 ), whereas peritumoral glutamate-glutamine recycling is potential marker invasion capacity pooled cohorts, linked secondary lesions. Our findings were validated by characterization each tumor, including cell density proliferation, infiltration, distant migration. study bodes well precision neuro-oncology, highlighting importance mapping better understand metabolic heterogeneity its links