BT-07 * MEASURING TUMOR METABOLISM IN DIFFUSE INTRINSIC PONTINE GIOMAS (DIPG) USING HYPERPOLARIZED CARBON-13 MR SPECTROSCOPIC IMAGING

Abstract

Diffuse intrinsic pontine gliomas (DIPGs) continue to have a very poor prognosis with a median survival rate of 9 months. The methods for assessing treatment response and tumor progression are based on radiographic response but conventional MRI is not sufficient for predicting clinical outcome. A recent first-in-human study using hyperpolarized 13C MR metabolic imaging showed the safety and feasibility of this technology for evaluating hyperpolarized pyruvate metabolism in humans. The purpose of this study was to demonstrate the feasibility of using hyperpolarized 13C metabolic imaging with [1-13C]pyruvate as a non-invasive imaging tool to evaluate in vivo metabolism in orthotopic brainstem xenografts injected with human DIPG cells. Primary human derived DIPG cells were implanted into the brainstem of athymic rats (n = 4). 3D magnetic resonance spectroscopic imaging (MRSI) data were acquired using a clinical 3T scanner with a custom-designed 1H/13C coil after the injection of hyperpolarized [1-13C]pyruvate solution. The hyperpolarized 13C MRSI data exhibited an abnormal 13C metabolism in the T2 lesions. The mean normalized lactate, normalized pyruvate and the ratio of lactate to pyruvate in the T2 hyperintense voxels were 3.1 ± 1.7, 1.5 ± 0.4 and 0.47 ± 0.2 (mean ± standard deviation), respectively, and significantly higher than the corresponding values from the contra-lateral hemisphere. The lactate signal in theses areas were highly elevated compared to the lactate signal in the normal appearing brain tissue from the supratentorial region. The metabolite quantification revealed the differentiation of lactate signal between tumor core, tissue in the periphery of tumor and tissue in the contra-lateral hemisphere. The corresponding H&E stained slides showed viable tumor that recapitulated the histopathology of a subset of high-grade pediatric astrocytomas. The results suggest that this technique may provide a unique non-invasive imaging tool that will be beneficial in the management of patients with DIPG.