Fixation method influences FLASH skin sparing in an in vivo leg model
Background and purpose: The FLASH effect, where ultra-high dose rate elicits a favourable normal tissue-sparing, has been shown in several preclinical studies. Study setup differences, for example fixation methods that affect blood flow, can influence radiation response but are unexplored for FLASH....
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Medical Journals Sweden
2025-08-01
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| Series: | Acta Oncologica |
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| Online Access: | https://medicaljournalssweden.se/actaoncologica/article/view/43972 |
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| author | Line Kristensen Cathrine Overgaard Jacob Johansen Anna Hansen Niels Bassler Per Poulsen Brita Sørensen |
| author_facet | Line Kristensen Cathrine Overgaard Jacob Johansen Anna Hansen Niels Bassler Per Poulsen Brita Sørensen |
| author_sort | Line Kristensen |
| collection | DOAJ |
| description | Background and purpose: The FLASH effect, where ultra-high dose rate elicits a favourable normal tissue-sparing, has been shown in several preclinical studies. Study setup differences, for example fixation methods that affect blood flow, can influence radiation response but are unexplored for FLASH. This study compared FLASH’s acute skin-sparing effect with two fixation methods: a glued fixation (no blood flow restriction) and taped fixation (slight blood flow restriction).
Patient/material and methods: Female CDF1 mice were irradiated on their hind foot using a glue-fixation or tape-fixation method. Glue-fixated mice were only taped during the glueing procedure and had a 10-min unrestricted period afterwards before irradiation, while tape-fixated mice were taped shortly before and throughout irradiation. Mice received single-dose irradiation (19–58 Gy) with either conventional dose rate (CONV, protons 0.06 Gy/s, electrons 0.16 Gy/s) or FLASH (electrons, 223–233 Gy/s). Differences in skin toxicity were analysed.
Results: CONV-treated tape-fixated mice required a 16–17% higher dose to induce skin toxicity relative to glued mice for both protons and electrons. Meanwhile, the fixation method did not affect FLASH-treated mice. The resulting electron FLASH-sparing effect was reduced by 18% due to the shift in radiosensitivity for CONV-treated mice.
Interpretation: CONV-treated tape-fixated mice were more radioresistant than the glue-fixated mice, consistent with the expected response to mild hypoxia. FLASH-treated mice were unaffected. These findings demonstrate the impact of fixation and, in turn, oxygen level on the differential CONV versus FLASH skin response. The results highlight the importance of minimal systemic influence on animals during FLASH studies.
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| format | Article |
| id | doaj-art-8e736e151e3745b1bcc83bc8d2d691a0 |
| institution | Kabale University |
| issn | 1651-226X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Medical Journals Sweden |
| record_format | Article |
| series | Acta Oncologica |
| spelling | doaj-art-8e736e151e3745b1bcc83bc8d2d691a02025-08-20T03:43:58ZengMedical Journals SwedenActa Oncologica1651-226X2025-08-016410.2340/1651-226X.2025.43972Fixation method influences FLASH skin sparing in an in vivo leg modelLine Kristensen0https://orcid.org/0000-0003-0924-475XCathrine Overgaard1https://orcid.org/0000-0002-8546-2735Jacob Johansen2Anna Hansen3Niels Bassler4https://orcid.org/0000-0002-4160-1078Per Poulsen5Brita Sørensen6Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDanish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDanish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDanish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDanish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkBackground and purpose: The FLASH effect, where ultra-high dose rate elicits a favourable normal tissue-sparing, has been shown in several preclinical studies. Study setup differences, for example fixation methods that affect blood flow, can influence radiation response but are unexplored for FLASH. This study compared FLASH’s acute skin-sparing effect with two fixation methods: a glued fixation (no blood flow restriction) and taped fixation (slight blood flow restriction). Patient/material and methods: Female CDF1 mice were irradiated on their hind foot using a glue-fixation or tape-fixation method. Glue-fixated mice were only taped during the glueing procedure and had a 10-min unrestricted period afterwards before irradiation, while tape-fixated mice were taped shortly before and throughout irradiation. Mice received single-dose irradiation (19–58 Gy) with either conventional dose rate (CONV, protons 0.06 Gy/s, electrons 0.16 Gy/s) or FLASH (electrons, 223–233 Gy/s). Differences in skin toxicity were analysed. Results: CONV-treated tape-fixated mice required a 16–17% higher dose to induce skin toxicity relative to glued mice for both protons and electrons. Meanwhile, the fixation method did not affect FLASH-treated mice. The resulting electron FLASH-sparing effect was reduced by 18% due to the shift in radiosensitivity for CONV-treated mice. Interpretation: CONV-treated tape-fixated mice were more radioresistant than the glue-fixated mice, consistent with the expected response to mild hypoxia. FLASH-treated mice were unaffected. These findings demonstrate the impact of fixation and, in turn, oxygen level on the differential CONV versus FLASH skin response. The results highlight the importance of minimal systemic influence on animals during FLASH studies. https://medicaljournalssweden.se/actaoncologica/article/view/43972FLASH radiotherapyultra-high dose ratenormal tissue sparingacute skin damagemurine normal tissues |
| spellingShingle | Line Kristensen Cathrine Overgaard Jacob Johansen Anna Hansen Niels Bassler Per Poulsen Brita Sørensen Fixation method influences FLASH skin sparing in an in vivo leg model Acta Oncologica FLASH radiotherapy ultra-high dose rate normal tissue sparing acute skin damage murine normal tissues |
| title | Fixation method influences FLASH skin sparing in an in vivo leg model |
| title_full | Fixation method influences FLASH skin sparing in an in vivo leg model |
| title_fullStr | Fixation method influences FLASH skin sparing in an in vivo leg model |
| title_full_unstemmed | Fixation method influences FLASH skin sparing in an in vivo leg model |
| title_short | Fixation method influences FLASH skin sparing in an in vivo leg model |
| title_sort | fixation method influences flash skin sparing in an in vivo leg model |
| topic | FLASH radiotherapy ultra-high dose rate normal tissue sparing acute skin damage murine normal tissues |
| url | https://medicaljournalssweden.se/actaoncologica/article/view/43972 |
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