PT  - JOURNAL ARTICLE
AU  - Autry, Adam W.
AU  - Kim, Yaewon
AU  - Dang, Duy
AU  - Chen, Hsin-Yu
AU  - Slater, James B.
AU  - Bok, Robert A.
AU  - Xu, Duan
AU  - Lupo, Janine M.
AU  - Gordon, Jeremy W.
AU  - Larson, Peder E.Z.
AU  - Vigneron, Daniel B.
AU  - Li, Yan
AU  - Chang, Susan M.
TI  - Clinical Translation of Hyperpolarized <sup>13</sup>C Metabolic Probes for Glioma Imaging
AID  - 10.3174/ajnr.A8726
DP  - 2025 Mar 05
TA  - American Journal of Neuroradiology
PG  - ajnr.A8726
4099  - http://www.ajnr.org/content/early/2025/03/05/ajnr.A8726.short
4100  - http://www.ajnr.org/content/early/2025/03/05/ajnr.A8726.full
AB  - 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.