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Open AccessArticle

Monitoring Early Changes in Tumor Metabolism in Response to Therapy Using Hyperpolarized 13C MRSI in a Preclinical Model of Glioma

1
Department of Medical Biophysics, Western University, London, ON, Canada
2
General Electric Healthcare, Toronto, ON, Canada
3
Department of Physics and Astronomy, Western University, London, ON, Canada
4
Department of Oncology, Western University, London, ON, Canada
5
Robarts Research Institute, Western University, London, ON, Canada
6
Ontario Institute for Cancer Research, Toronto, ON, Canada
*
Author to whom correspondence should be addressed.
Tomography 2020, 6(3), 290-300; https://doi.org/10.18383/j.tom.2020.00024
Received: 8 June 2020 / Revised: 5 July 2020 / Accepted: 11 August 2020 / Published: 1 September 2020
This study shows the use of hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) to assess therapeutic efficacy in a preclinical tumor model. 13C-labeled pyruvate was used to monitor early changes in tumor metabolism based on the Warburg effect. High-grade malignant tumors exhibit increased glycolytic activity and lactate production to promote proliferation. A rodent glioma model was used to explore altered lactate production after therapy as an early imaging biomarker for therapeutic response. Rodents were surgically implanted with C6 glioma cells and separated into 4 groups, namely, no therapy, radiotherapy, chemotherapy and combined therapy. Animals were imaged serially at 6 different time points with magnetic resonance imaging at 3 T using hyperpolarized [1-13C]pyruvate MRSI and conventional 1H imaging. Using hyperpolarized [1-13C]pyruvate MRSI, alterations in tumor metabolism were detected as changes in the conversion of lactate to pyruvate (measured as Lac/Pyr ratio) and compared with the conventional method of detecting therapeutic response using the Response Evaluation Criteria in Solid Tumors. Moreover, each therapy group expressed different characteristic changes in tumor metabolism. The group that received no therapy showed a gradual increase of Lac/Pyr ratio within the tumor. The radiotherapy group showed large variations in tumor Lac/Pyr ratio. The chemo- and combined-therapy groups showed a statistically significant reduction in tumor Lac/Pyr ratio; however, only combined therapy was capable of suppressing tumor growth, which resulted in low endpoint mortality rate. Hyperpolarized 13C MRSI detected a prompt reduction in Lac/Pyr ratio as early as 2 days post combined chemo- and radiotherapies.
Keywords: hyperpolarized 13C; pyruvate; tumor metabolism; therapeutic response; glioma hyperpolarized 13C; pyruvate; tumor metabolism; therapeutic response; glioma
MDPI and ACS Style

Lim, H.; Martínez-Santiesteban, F.; Jensen, M.D.; Chen, A.; Wong, E.; Scholl, T.J. Monitoring Early Changes in Tumor Metabolism in Response to Therapy Using Hyperpolarized 13C MRSI in a Preclinical Model of Glioma. Tomography 2020, 6, 290-300. https://doi.org/10.18383/j.tom.2020.00024

AMA Style

Lim H, Martínez-Santiesteban F, Jensen MD, Chen A, Wong E, Scholl TJ. Monitoring Early Changes in Tumor Metabolism in Response to Therapy Using Hyperpolarized 13C MRSI in a Preclinical Model of Glioma. Tomography. 2020; 6(3):290-300. https://doi.org/10.18383/j.tom.2020.00024

Chicago/Turabian Style

Lim, Heeseung; Martínez-Santiesteban, Francisco; Jensen, Michael D.; Chen, Albert; Wong, Eugene; Scholl, Timothy J. 2020. "Monitoring Early Changes in Tumor Metabolism in Response to Therapy Using Hyperpolarized 13C MRSI in a Preclinical Model of Glioma" Tomography 6, no. 3: 290-300. https://doi.org/10.18383/j.tom.2020.00024

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