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

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Metabolites
• Subjects: cancer metabolism; dynamic nuclear polarization; glycolysis; immune system; magnetic resonance imaging; radiation
• Online Access: https://www.mdpi.com/2218-1989/11/8/518

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 (<i>k</i>_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.