DIPG-16. NONINVASIVE ASSESSMENT OF TREATMENT RESPONSE FOR DIFFUSE INTRINSIC PONTINE GLIOMA USING HYPERPOLARIZED 13C METABOLIC IMAGING

INTRODUCTION: It remains often challenging on conventional MR imaging to distinguish between true versus pseudo-progression in children with diffuse intrinsic pontine glioma (DIPG). Hyperpolarized 13C MR metabolic imaging is a promising new technology that provides a non-invasive imaging approach to monitor changes in functional properties of tumors. We have shown previously that 13C-pyruvate can be used to monitor the rate and magnitude of conversion to 13C-lactate, which is elevated in tumors due to increased activity of the enzyme lactate dehydrogenase (LDH). We hypothesize that levels of hyperpolarized lactate, detected by monitoring hyperpolarized pyruvate metabolism using 13C MR metabolic imaging, will be modulated in response to therapy and might be a suitable noninvasive biomarker of therapy response. METHODS: In vitro imaging studies were performed by treating primary DIPG cells (SF8628) with panobinostat and assessing lactate to pyruvate ratios using 13C MR metabolic imaging. Activity of LDH was assessed using spectrophotometric assays. For in vivo studies, SF8628 cells were injected directly into the pons of rats and hyperpolarized 13C imaging was used to assess lactate/pyruvate ratios after therapy with 8 Gy radiation (n=3) compared to control animals (n=3). RESULTS: Pyruvate to lactate conversion was significantly reduced in the panobinostat-treated DIPG cells compared to control (p=0.03). As expected, the reduced lactate signal was associated with decreased levels of LDHA activity compared to control (p=0.03). Rats treated with radiation showed a decrease in lactate/pyruvate at day 2 and 4 compared to baseline, whereas control rats showed a continuous increase in lactate/pyruvate at day 2 and 4 compared to baseline. CONCLUSION: The results from this study suggest that hyperpolarized 13C metabolic imaging may be a suitable imaging marker to monitor therapy response in DIPG. A phase 1 study trial testing this imaging modality is ongoing.