Game Changer Grant Awarded to Pavithra Viswanath and Sabine Mueller

Children with DMGs are typically treated with radiation and novel therapies that are in clinical trials. Due to the critical anatomical location and their tendency to infiltrate the brain in a diffuse manner, disease progression in children with DMGs is heavily dependent on non-invasive magnetic resonance imaging (MRI). However, MRI does not reliably determine whether a child with DMG is responding to treatment. As a result, physicians, patients, and their parents are left in a “black box” after starting therapy and precious time is wasted because of the inability to correctly determine whether the patient is responding. We need newer and better non-invasive tools for measuring DMG response to therapy early on in the course of treatment.

Tumor tissues take up more glucose relative to surrounding normal brain and convert this glucose almostexclusively to the metabolite lactate rather than glutamate. This property, known as the Warburg effect, provides the unique opportunity to use a stable non-radioactive form of glucose (deuterated glucose) to track tumor growth in vivo. Our preliminary studies suggest that alterations in deuterated glucose metabolism are seen within 5 days of radiotherapy in DMG-bearing mice, when no changes can be seen on MRI. Based on these results, we will determine whether deuterated glucose can be used to visualize metabolically active tumor tissue (Aim 1) and obtain an early readout of response to therapy (Aim 2) in DMG-bearing mice. Our studies will improve patient care by allowing physicians to identify patients who are responding to standard radiation therapy at early timepoints when a switch to a novel targeted therapy holds the possibility of improving patient survival. Our studies will improve clinical research and drug development by allowing physicians to decide whether the drug under evaluation provides meaningful benefit at early timepoints. Importantly, deuterated glucose is a safe, orally administered, brain penetrant agent and its use is technologically simple and readily integrated into existing MR scanners. We, therefore, anticipate that deuterated glucose can be translated to DMG patients within a short period of time if our studies are supportive.