Pilot Study of Hyperpolarized ¹³C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers

Background and purpose: Pediatric CNS tumors commonly present challenges for radiographic interpretation on conventional MR imaging. This study sought to investigate the safety and tolerability of hyperpolarized carbon-13 (HP-¹³C) metabolic imaging in pediatric patients with brain tumors.

Materials and methods: Pediatric patients 3 to 18 years of age who were previously diagnosed with a brain tumor and could undergo MR imaging without sedation were eligible to enroll in this safety study of HP [1-¹³C]pyruvate. Participants received a one-time injection of HP [1-¹³C]pyruvate and were imaged using dynamic HP-¹³C MR imaging. We assessed 2 dose levels: 0.34 mL/kg and the highest tolerated adult dose of 0.43 mL/kg. Participants were monitored throughout imaging and for 60 minutes postinjection, including pre- and postinjection electrocardiograms and vital sign measurements.

Results: Between February 2017 and July 2019, ten participants (9 males; median age, 14 years; range, 10-17 years) were enrolled, of whom 6 completed injection of HP [1-¹³C]pyruvate and dynamic HP-¹³C MR imaging. Four participants failed to undergo HP-¹³C MR imaging due to technical failures related to generating HP [1-¹³C]pyruvate or MR imaging operability. HP [1-¹³C]pyruvate was well-tolerated in all participants who completed the study, with no dose-limiting toxicities or adverse events observed at either 0.34 (n = 3) or 0.43 (n = 3) mL/kg. HP [1-¹³C]pyruvate demonstrated characteristic conversion to [1-¹³C]lactate and [¹³C]bicarbonate in the brain. Due to poor accrual, the study was closed after only 3 participants were enrolled at the highest dose level.

Conclusions: Dynamic HP-¹³C MR imaging was safely performed in 6 pediatric patients with CNS tumors and demonstrated HP [1-¹³C]pyruvate brain metabolism.