TMET-12. HYPERPOLARIZED Δ- [1-13C] GLUCONOLACTONE IMAGING VISUALIZES TERT-ASSOCIATED CHANGES IN DYNAMIC PENTOSE PHOSPHATE PATHWAY METABOLISM IN GLIOBLASTOMA

Abstract BACKGROUND TERT promoter mutations are a hallmark of glioblastoma (GBM). We recently reported that the expression and its upstream transcriptional factor, GABPB1, strongly correlated with redox in GBM mutations. However, further imaging biomarkers which visualize redox-associated metabolism needed. Here we demonstrate 13C magnetic resonance spectroscopy (MRS) hyperpolarized δ-[1-13C] gluconolactone is useful tool to changes dynamic pentose phosphate pathway (PPP) reflect TERT-associated GBM. METHODS U251 human cells stably expressing shRNA targeting or GABPB1 were compared controls. Doxycyclin-inducible shTERT shGABPB1 also examined. For vivo studies, injected into immunodeficient rat brains tumors confirmed by T2-weighted MRI. was polarized using Hypersense DNP polarizer live tumor-bearing rats. 13C-MRS acquired 500MHz Agilent spectrometer analyzed Mnova Matlab software. vivo13C-MRS spectra 3T Bruker scanner spectral spatial echo-planar spectroscopic sequence. Spectral signal noise improved Tensor denoising. Spectra processed custom-written script. RESULTS Hyperpolarized 6-phosphogluconolactone (6PG), metabolic product from via PPP, significantly reduced silenced control both models. The positive correlation between 6PG level linear regression analysis. production tumor models GABPB1-silenced CONCLUSION successfully visualized PPP model vivo. potential for monitoring