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Hyperpolarized δ-[1-13C]gluconolactone detects response to chemotherapy in brain tumors in vivo
Georgios Batsios1, Celine Taglang1, Anne Marie Gillespie1, Peder Larson1, Sabrina M Ronen1, and Pavithra Viswanath1
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States
We show that assessment of glucose metabolism via the pentose phosphate pathway using hyperpolarized δ-[1-13C]gluconolactone informs on early response to chemotherapy in preclinical glioma models. Our results have the potential to enhance therapy assessment for glioma patients.
Hyperpolarized δ-[1-13C]gluconolactone informs on early response to TMZ treatment in vivo. Top: representative metabolic maps from a BT88-bearing rat pre-treatment with TMZ. T2 weighted MRI (A), heatmap of SNR of hyperpolarized δ-[1-13C]gluconolactone (B) and heatmap of 6PG/δ-[1-13C]gluconolactone ratio (C). Bottom: metabolic maps from a BT88-bearing rat post-treatment with TMZ. T2 weighted MRI (D), heatmap of SNR of hyperpolarized δ-[1-13C]gluconolactone (E) and heatmap of 6PG/δ-[1-13C]gluconolactone ratio (F). Tumor is delineated in white.
Hyperpolarized δ-[1-13C]gluconolactone can monitor response to temozolomide (TMZ) in glioma cells. Representative 13C-MRS spectral array (A) and summed 13C spectra (B) showing 6PG production from hyperpolarized δ-[1-13C]gluconolactone in live U87 cells. Effect of TMZ on 6PG production in U87 (C) and GS2 (D) cells (N=3).