Characterization of the Intestinal Metabolic Profiles Following Photon FLASH Irradiation

Area of Science:

• Oncology
• Metabolomics
• Radiation Biology

Background:

• Ultra-high dose rate radiotherapy, known as FLASH radiotherapy, is a rapidly advancing area in cancer treatment research.
• Understanding the biological effects of FLASH radiotherapy is crucial for its clinical application.

Purpose of the Study:

• To identify metabolic biomarkers in intestinal contents following photon FLASH irradiation.
• To investigate the dose-dependent metabolic alterations induced by FLASH radiotherapy.

Main Methods:

• C57BL/6J mice were subjected to varying doses of photon FLASH irradiation (0-14 Gy).
• Intestinal contents were analyzed using liquid chromatography-mass spectrometry (LC-MS) 3.5 days post-irradiation.
• Metabolomic profiling was performed to identify differential metabolites and perturbed pathways.

Main Results:

• 25 differential metabolites were identified across different irradiation doses.
• 3-hydroxyanthranilate showed a dose-dependent positive correlation, while 13 metabolites, including guanosine and adenosine monophosphate, showed a negative correlation with FLASH dose.
• Enrichment analysis revealed significant alterations in PI3K-AKT signaling, tyrosine metabolism, and purine metabolism.

Conclusions:

• Photon FLASH radiotherapy induces distinct metabolic signatures in the intestine.
• These metabolic insights can guide the optimization of FLASH radiotherapy protocols.
• The findings contribute to enhancing the therapeutic ratio of FLASH radiotherapy.