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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398834/ https://www.ncbi.nlm.nih.gov/pubmed/34436459 http://dx.doi.org/10.3390/metabo11080518 |
Sumario: | 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-(13)C]pyruvate is transported by the monocarboxylate transporter (MCT) into cells and converted into [1-(13)C]lactate by lactate dehydrogenase (LDH). To capture the early glycolytic alterations in the irradiated cancer and immune cells, we designed a preliminary DNP (13)C-MRI study by using hyperpolarized [1-(13)C]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 (13)C-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 (13)C-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. |
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