Monitoring Early Glycolytic Flux Alterations Following Radiotherapy in Cancer and Immune Cells: Hyperpolarized Carbon-13 Magnetic Resonance Imaging Study

Ying-Chieh Lai; Ching-Yi Hsieh; Kuan-Ying Lu; Cheng-Hsuan Sung; Hung-Yao Ho; Mei-Ling Cheng; Albert P Chen; Shu-Hang Ng; Fang-Hsin Chen; Gigin Lin

doi:10.3390/metabo11080518

Monitoring Early Glycolytic Flux Alterations Following Radiotherapy in Cancer and Immune Cells: Hyperpolarized Carbon-13 Magnetic Resonance Imaging Study

Metabolites. 2021 Aug 6;11(8):518. doi: 10.3390/metabo11080518.

Authors

Ying-Chieh Lai^{1

2}, Ching-Yi Hsieh^{2

3

4}, Kuan-Ying Lu^{1

2}, Cheng-Hsuan Sung^{3

4}, Hung-Yao Ho^{2

5

6

7}, Mei-Ling Cheng^{2

5

6

8}, Albert P Chen⁹, Shu-Hang Ng^{1

4}, Fang-Hsin Chen^{4

10

11}, Gigin Lin^{1

2

3

4}

Affiliations

¹ Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan.
² Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan.
³ Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan.
⁴ Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 333, Taiwan.
⁵ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁶ Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan.
⁷ Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁸ Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁹ GE Healthcare, Toronto, ON M5V 3Y3, Canada.
¹⁰ Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan.
¹¹ Department of Radiation Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan.

Abstract

Alterations in metabolism following radiotherapy affect therapeutic efficacy, although the mechanism underlying such alterations is unclear. A new imaging technique-named dynamic nuclear polarization (DNP) carbon-13 magnetic resonance imaging (MRI)-probes the glycolytic flux in a real-time, dynamic manner. The [1-¹³C]pyruvate is transported by the monocarboxylate transporter (MCT) into cells and converted into [1-¹³C]lactate by lactate dehydrogenase (LDH). To capture the early glycolytic alterations in the irradiated cancer and immune cells, we designed a preliminary DNP ¹³C-MRI study by using hyperpolarized [1-¹³C]pyruvate to study human FaDu squamous carcinoma cells, HMC3 microglial cells, and THP-1 monocytes before and after irradiation. The pyruvate-to-lactate conversion rate (k_PL [Pyr.]) calculated by kinetic modeling was used to evaluate the metabolic alterations. Western blotting was performed to assess the expressions of LDHA, LDHB, MCT1, and MCT4 proteins. Following irradiation, the pyruvate-to-lactate conversion rates on DNP ¹³C-MRI were significantly decreased in the FaDu and the HMC3 cells but increased in the THP-1 cells. Western blot analysis confirmed the similar trends in LDHA and LDHB expression levels. In conclusion, DNP ¹³C-MRI non-invasively captured the different glycolytic alterations among cancer and immune systems in response to irradiation, implying its potential for clinical use in the future.

Keywords: cancer metabolism; dynamic nuclear polarization; glycolysis; immune system; magnetic resonance imaging; radiation.

Abstract

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