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

Metabolites

Hung-Yao Ho¹  Ching-Yi Hsieh¹  Mei-Ling Cheng¹  Shu-Hang Ng²  Ying-Chieh Lai²  Gigin Lin²  Kuan-Ying Lu²  Fang-Hsin Chen³  Albert P. Chen⁴  Cheng-Hsuan Sung⁵ 

[1] Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan;Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan;Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 333, Taiwan;GE Healthcare, Toronto, ON M5V 3Y3, Canada;Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan;

关键词: cancer metabolism;    dynamic nuclear polarization;    glycolysis;    immune system;    magnetic resonance imaging;    radiation;   

DOI  :  10.3390/metabo11080518

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown