Infrared microspectroscopy to elucidate the underlying biomolecular mechanisms of FLASH radiotherapy
Martínez-Rovira, Immaculada (Universitat Autònoma de Barcelona. Departament de Física)
Montay-Gruel, Pierre (University of Antwerp (Bèlgica))
Petit, Benoît (Lausanne University Hospital (Suïssa))
Leavitt, Ron J. (Lausanne University Hospital)
González-Vegas, Roberto (Universitat Autònoma de Barcelona. Departament de Física)
Froidevaux, Pascal (Lausanne University Hospital (Suïssa))
Juchaux, Marjorie (Centre de recherche d'Orsay. Institut Curie)
Prezado, Yolanda (Centre de recherche d'Orsay. Institut Curie)
Yousef, Ibraheem (ALBA Laboratori de Llum de Sincrotró)
Vozenin, Marie-Catherine (Hôpitaux Universitaires de Genève)

Data:	2024
Resum:	FLASH-radiotherapy (FLASH-RT) is an emerging modality that uses ultra-high dose rates of radiation to enable curative doses to the tumor while preserving normal tissue. The biological studies showed the potential of FLASH-RT to revolutionize radiotherapy cancer treatments. However, the complex biological basis of FLASH-RT is not fully known yet. Aim: Within this context, our aim is to get deeper insights into the biomolecular mechanisms underlying FLASH-RT through Fourier Transform Infrared Microspectroscopy (FTIRM). C57Bl/6J female mice were whole brain irradiated at 10 Gy with the eRT6-Oriatron system. 10 Gy FLASH-RT was delivered in 1 pulse of 1. 8μs and conventional irradiations at 0. 1 Gy/s. Brains were sampled and prepared for analysis 24 h post-RT. FTIRM was performed at the MIRAS beamline of ALBA Synchrotron. Infrared raster scanning maps of the whole mice brain sections were collected for each sample condition. Hyperspectral imaging and Principal Component Analysis (PCA) were performed in several regions of the brain. PCA results evidenced a clear separation between conventional and FLASH irradiations in the 1800-950 cm region, with a significant overlap between FLASH and Control groups. An analysis of the loading plots revealed that most of the variance accounting for the separation between groups was associated to modifications in the protein backbone (Amide I). This protein degradation and/or conformational rearrangement was concomitant with nucleic acid fragmentation/condensation. Cluster separation between FLASH and conventional groups was also present in the 3000-2800 cm region, being correlated with changes in the methylene and methyl group concentrations and in the lipid chain length. Specific vibrational features were detected as a function of the brain region. This work provided new insights into the biomolecular effects involved in FLASH-RT through FTIRM. Our results showed that beyond nucleic acid investigations, one should take into account other dose-rate responsive molecules such as proteins, as they might be key to understand FLASH effect.
Nota:	Altres ajuts: acords transformatius de la UAB
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	FLASH radiotherapy ; Infrared microspectroscopy ; Radiobiological studies
Publicat a:	Radiotherapy and oncology, Vol. 196 (july 2024) , p. 110238, ISSN 1879-0887

DOI: 10.1016/j.radonc.2024.110238
PMID: 38527626

10 p, 4.3 MB

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