In vivo measurements of change in tissue oxygen level during irradiation reveal novel dose rate dependence.
Radiother Oncol
; 201: 110539, 2024 Sep 17.
Article
em En
| MEDLINE
| ID: mdl-39299575
ABSTRACT
BACKGROUND AND PURPOSE:
This study aimed to investigate the radiochemical oxygen depletion (ROD) in vivo by directly measuring oxygen levels in various mouse tissues during ultra-high dose rate (UHDR) irradiation at clinically relevant doses and dose rates. MATERIALS ANDMETHODS:
Mice bearing subcutaneous human glioblastoma (U-87 MG) tumors were used for tumor and normal tissue (skin, muscle, brain) measurements. An oxygen-sensitive phosphorescent probe (Oxyphor PtG4) was injected into the tissues, and oxygen levels were monitored using a fiberoptic phosphorometer during UHDR irradiation with a 6 MeV electron linear accelerator (LINAC). Dose escalation experiments (10-40 Gy) were performed at a dose rate of 1300 Gy/s, and dose rate escalation experiments were conducted at a fixed dose of 40 Gy with dose rates ranging from 2 to 101 Gy/s.RESULTS:
Radiation-induced change in tissue oxygenation (ΔpO2) increased linearly with dose and correlated with baseline tissue oxygenation levels in the range of 0 - 30 mmHg. At higher baseline tissue oxygenation levels, such as those observed in muscle and brain, there was no corresponding increase in ΔpO2. When we modulated dose rate, ΔpO2 increased steeply up to â¼ 20 Gy/s and plateaued thereafter. The relationship between ΔpO2 and dose rate showcases the interplay between ROD and reoxygenation.CONCLUSION:
While UHDR irradiation induces measurable oxygen depletion in tissues, the observed changes in oxygenation levels do not support the hypothesis that ROD-induced radioresistance is responsible for the FLASH tissue-sparing effect at clinically relevant doses and dose rates. These findings highlight the need for further investigation into alternative mechanisms underlying the FLASH effect.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Radiother Oncol
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Irlanda