BIMG-05. TO BE OR NOT TO BE GLYCOLYTIC: DEUTERATED GLUCOSE-BASED ASSESSMENT OF THE WARBURG EFFECT ALLOWS NON-INVASIVE IMAGING OF TUMOR BURDEN AND TREATMENT RESPONSE IN MUTANT IDH GLIOMAS <i>IN VIVO</i>
Bibliographic record
Abstract
Abstract The Warburg effect, characterized by elevated glucose uptake and flux to lactate, is a metabolic hallmark of cancer. Recent studies have identified deuterium 2H-magnetic resonance spectroscopy (MRS) using 6,6’-2H-glucose as a novel method of imaging the Warburg effect in high-grade primary glioblastomas (GBMs). However, its utility for imaging low-grade gliomas has not been tested. The goal of this study was to determine whether 6,6’-2H-glucose can be used for imaging tumor burden and treatment response in mutant isocitrate dehydrogenase (IDHmut) low-grade gliomas in vivo. We examined mice bearing orthotopic tumors of the patient-derived BT257 astrocytoma model. 1H-MRS, providing a readout of steady-state metabolite levels, confirmed the presence of 2-hydroxyglutarate, the product of IDHmut, in BT257 tumor tissue but not normal brain. Previous studies comparing IDHmut gliomas with GBMs suggest that IDHmut gliomas undergo lactate dehydrogenase silencing, potentially leading to a non-glycolytic phenotype. Nevertheless, our results indicated that, compared to normal brain, glucose uptake and concomitant flux to lactate were significantly higher in BT257 tumor tissue. Importantly, 6,6’-2H-glucose metabolism to lactate was observed in BT257 tumor-bearing mice, but not tumor-free mice. Furthermore, imaging studies confirmed spatial localization of lactate production to the tumor vs. contralateral normal brain. We then examined the ability of 6,6’-2H-glucose to assess treatment response. Poly-(adenosine 5′-diphosphate-ribose) polymerase inhibitors (PARPi) inhibit IDHmut glioma growth and are in clinical trials for IDHmut glioma patients. Treatment with the PARPi niraparib reduced 6,6’-2H-glucose flux to lactate in BT257 tumor-bearing mice. Importantly, this reduction was observed at early time-points when no difference in tumor volume could be detected using anatomical imaging, pointing to the ability of 6,6’-2H-glucose to assess pseudoprogression. Collectively, our results suggest that IDHmut gliomas display a glycolytic phenotype amenable to non-invasive 2H-MRS-based imaging of tumor burden and treatment response.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".