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

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-C-13]pyruvate is transported by the monocarboxylate transporter (MCT) into cells and converted into [1-C-13]lactate by lactate dehydrogenase (LDH). To capture the early glycolytic alterations in the irradiated cancer and immune cells, we designed a preliminary DNP C-13-MRI study by using hyperpolarized [1-C-13]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 C-13-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 C-13-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.

Automated summary

The study utilized a new imaging technique, DNP C-13-MRI, to explore the metabolic effects of radiation on cancer cells and immune cells. The results showed significant changes in glycolytic flux rates in different types of cells after irradiation, suggesting the potential clinical utility of DNP C-13-MRI for future treatments.