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Clinical Translation of Hyperpolarized 13C Metabolic Probes for Glioma Imaging

Adam W. Autry, Yaewon Kim, Duy Dang, Hsin-Yu Chen, James B. Slater, Robert A. Bok, Duan Xu, Janine M. Lupo, Jeremy W. Gordon, Peder E.Z. Larson, Daniel B. Vigneron, Yan Li and Susan M. Chang
American Journal of Neuroradiology March 2025, ajnr.A8726; DOI: https://doi.org/10.3174/ajnr.A8726
Adam W. Autry
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Yaewon Kim
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Duy Dang
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Hsin-Yu Chen
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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James B. Slater
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Robert A. Bok
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Duan Xu
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Janine M. Lupo
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Jeremy W. Gordon
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Peder E.Z. Larson
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Daniel B. Vigneron
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Yan Li
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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Susan M. Chang
From the Department of Radiology and Biomedical Imaging (A.W.A., Y.K., D.D., H.C., J.B.S., R.A.B., D.X., J.M.L., J.W.G., P.E.Z.L., D.B.V., Y.L.), Department of Neurological Surgery (D.B.V., S.M.C.), Department of Bioengineering and Therapeutic Sciences (D.B.V.) University of California San Francisco, San Francisco, CA, USA
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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.

Footnotes

  • Authors declare no conflicts of interest.

  • © 2025 by American Journal of Neuroradiology

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Cite this article
Accepted Manuscript
Adam W. Autry, Yaewon Kim, Duy Dang, Hsin-Yu Chen, James B. Slater, Robert A. Bok, Duan Xu, Janine M. Lupo, Jeremy W. Gordon, Peder E.Z. Larson, Daniel B. Vigneron, Yan Li, Susan M. Chang
Clinical Translation of Hyperpolarized 13C Metabolic Probes for Glioma Imaging
American Journal of Neuroradiology Mar 2025, ajnr.A8726; DOI: 10.3174/ajnr.A8726

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Accepted Manuscript
Clinical Translation of Hyperpolarized 13C Metabolic Probes for Glioma Imaging
Adam W. Autry, Yaewon Kim, Duy Dang, Hsin-Yu Chen, James B. Slater, Robert A. Bok, Duan Xu, Janine M. Lupo, Jeremy W. Gordon, Peder E.Z. Larson, Daniel B. Vigneron, Yan Li, Susan M. Chang
American Journal of Neuroradiology Mar 2025, ajnr.A8726; DOI: 10.3174/ajnr.A8726
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