Clinical Translation of Hyperpolarized ¹³C Metabolic Probes for Glioma Imaging

SUMMARY: Hyperpolarized carbon-13 (HP-¹³C) MRI enables the real-time measurement of dynamic metabolism by utilizing molecular probes whose magnetization has been transiently enhanced via dynamic nuclear polarization of ¹³C labels. Based on preclinical and clinical investigations demonstrating Warburg-related metabolic dysfunction and tricarboxylic acid (TCA)-cycle alterations in gliomas, HP-¹³C techniques appear very promising for overcoming conventional challenges to evaluating tumor burden and extent, early therapeutic response, and progression among patients noninvasively. This article surveys the multifaceted translational development of HP-¹³C MRI in the context of glioma imaging, while emphasizing innovation concerning the pharmacy production of hyperpolarized (HP) probes—[1-¹³C]/[2-¹³C]-pyruvate and [1-¹³C,5-¹²C]-α-ketoglutarate—that serve as nonradioactive metabolic contrast agents. Borrowing from practical experience, we present specific probe indications for isocitrate dehydrogenase (IDH)-wild-type glioblastomas and IDH-mutant gliomas together with example data to show the targeted, pathway-dependent function of these agents and their utility. Additional information pertaining to HP-¹³C hardware, acquisition, and postprocessing techniques provides an overview of the imaging methodology as it is currently performed at a leading institution. Considering the developing markers for progressive disease in glioblastomas and rapidly advancing capability, this unique imaging technology appears poised for translational impact following further evaluation.