Clinical Translation of Hyperpolarized ¹³C Metabolic Probes for Glioma Imaging

ABSTRACT

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 pre-clinical and clinical investigations demonstrating Warburg-related metabolic dysfunction and tricarboxylic acid (TCA)-cycle alterations in gliomas, HP¹³C techniques appear very promising for overcoming conventional challenges to evaluating tumor burden and extent, early therapeutic response and progression among patients non-invasively. This article surveys the multi-faceted translational development of HP-¹³C MRI in the context of glioma imaging, while emphasizing innovation concerning the pharmacy production of HP probes – [1-¹³C]/[2-¹³C]-pyruvate and [1-¹³C,5-¹²C]-alpha-ketoglutarate – that serve as non-radioactive metabolic contrast agents. Borrowing from practical experience, we present specific probe indications for isocitrate dehydrogenase (IDH)-wildtype 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 post-processing 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.

ABBREVIATIONS: 2-HG = D-2-hydroxyglutarate; α-KG = alpha-ketoglutarate; CSI = chemical shift imaging; d-DNP = dissolution-dynamic nuclear polarization; EPI = echo-planar imaging; EPSI = echo-planar spectroscopic imaging; IDHm = isocitrate dehydrogenasemutant; IR-SPGR = inversion recovery-prepared fast spoiled gradient-recalled (imaging); LrGGs = lower-grade gliomas; NMR = nuclear magnetic resonance; OGC = oxoglutarate carrier; PHIP = parahydrogen-induced polarization; SNR = signal-to-noise ratio; TCA cycle = tricarboxylic acid cycle; WHO = World Health Organization.