HG-117: ASSESSING THE RESPONSE OF DIFFUSE INTRINSIC PONTINE GLIOMA TO PANOBINOSTAT USING HYPERPOLARIZED ¹³C MAGNETIC RESONANCE METABOLIC IMAGING

INTRODUCTION: One of the challenges in managing children with DIPG is the lack of non-invasive imaging biomarkers for monitoring response to therapy. Panobinostat is one of the promising drugs for the treatment of DIPG, and has shown anti-tumor effect in a recent in vivo study. This study aimed to develop clinically translatable metabolic imaging biomarkers for assessing the response of DIPG to panobinostat. We hypothesized that levels of hyperpolarized (HP) [1-¹³C]-lactate, detected by monitoring HP [1-¹³C]-pyruvate metabolism using ¹³C MR metabolic imaging, will be modulated in responding DIPG. METHODS: Vehicle- (n = 3) and panobinostat-treated (4 nM for 72hr, n = 2) K27M.H3 mutant DIPG cells were encapsulated in alginate microspheres and loaded in a 5mm NMR tube connected to a perfusion bioreactor system. A mixture of 7.5 µL of [1-¹³C]-pyruvate, 15mM trityl radical and 1.5mM Gd-DOTA were polarized using a HyperSense system. HP ¹³C spectra were acquired every 3s for a total of 5 min in a 500 MHz spectrometer using a 30° flip angle. Lactate levels were determined by normalizing the lactate area-under-the-curve (AUC) to the pyruvate AUC and the level of cell viability that was assessed by estimating the amount of β-NTP from ³¹P spectra. RESULTS AND DISCUSSION: HP ¹³C pyruvate to lactate conversion was reduced in the responding DIPG cells compared to control. Normalized lactate for treated (1.22 ± 0.44) was smaller than normalized lactate for control (4.02 ± 0.93, p = 0.03). The results from this study show that this novel metabolic imaging method may provide a non-invasive surrogate biomarker of response to panobinostat.