Detection of early response to temozolomide treatment in brain tumors using hyperpolarized 13C MR metabolic imaging

Authors

  • Ilwoo Park PhD,

    Corresponding author
    1. Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
    • 1700 4th St., Rm. BH-303, San Francisco, CA 94158
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  • Robert Bok MD,

    1. Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
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  • Tomoko Ozawa MD, PhD,

    1. Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, California, USA
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  • Joanna J. Phillips MD, PhD,

    1. Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, California, USA
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  • C. David James PhD,

    1. Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, California, USA
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  • Daniel B. Vigneron PhD,

    1. Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
    2. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA
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  • Sabrina M. Ronen PhD,

    1. Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
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  • Sarah J. Nelson PhD

    1. Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
    2. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA
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Abstract

Purpose:

To demonstrate the feasibility of using DNP hyperpolarized [1-13C]-pyruvate to measure early response to temozolomide (TMZ) therapy using an orthotopic human glioblastoma xenograft model.

Materials and Methods:

Twenty athymic rats with intracranial implantation of human glioblastoma cells were divided into two groups: one group received an oral administration of 100 mg/kg TMZ (n = 10) and the control group received vehicle only (n = 10). 13C 3D magnetic resonance spectroscopic imaging (MRSI) data were acquired following injection of 2.5 mL (100 mM) hyperpolarized [1-13C]-pyruvate using a 3T scanner prior to treatment (day D0), at D1 (days from treatment) or D2.

Results:

Tumor metabolism as assessed by the ratio of lactate to pyruvate (Lac/Pyr) was significantly altered at D1 for the TMZ-treated group but tumor volume did not show a reduction until D5 to D7. The percent change in Lac/Pyr from baseline was statistically different between the two groups at D1 and D2 (P < 0.008), while percent tumor volume was not (P > 0.2).

Conclusion:

The results from this study suggest that metabolic imaging with hyperpolarized [1-13C]-pyruvate may provide a unique tool that clinical neuro-oncologists can use in the future to monitor tumor response to therapy for patients with brain tumors. J. Magn. Reson. Imaging 2011;33:1284–1290. © 2011 Wiley-Liss, Inc.

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