Background and Aims

Since the oxygen depletion hypothesis has been recently challenged, the setup of a new joint project dedicated to an alternative mechanistic explanation of the FLASH effect, presently submitted to the Italian Association for Cancer Research (AIRC), will be presented. Our approach is a bottom up analysis linking radiation chemical based radicals description and DNA damage modeling studies. This should enable us to predict the irradiation parameters of absolute dose, and dose rate for which the effect could be verified.

Methods

We will develop point-like and two dimensional optical based methods for FLASH real time dosimetry using Cerenkov and radioluminescence light.

In a second phase a multiscale mechanistic description of ultrahigh dose rate induced damage including oxygen interplay and reactive oxygen species production and reactions will be developed. Our approach is based on chemical track structure Monte Carlo simulations and dedicated extensions of analytical biophysical models.

Results

We expect to obtain:

-Real time dosimetric methods to monitor FLASH beams for cells and mice irradiations. The same methods can be also translated to monitor FLASH delivery to human patients.

-A refined mechanistic description of the FLASH effect starting from basic radiation chemistry concepts in a biological environment. We will also provide in vitro and in vivo validation tests using two types of FLASH beams.

Conclusions

This work will contribute to unraveling the basic biological mechanisms of the FLASH effect and, at the same time, it will provide accurate real time dosimetric tools not available at the moment.

Background and Aims

Since the oxygen depletion hypothesis has been recently challenged, the setup of a new joint project dedicated to an alternative mechanistic explanation of the FLASH effect, presently submitted to the Italian Association for Cancer Research (AIRC), will be presented. Our approach is a bottom up analysis linking radiation chemical based radicals description and DNA damage modeling studies. This should enable us to predict the irradiation parameters of absolute dose, and dose rate for which the effect could be verified.

Methods

We will develop point-like and two dimensional optical based methods for FLASH real time dosimetry using Cerenkov and radioluminescence light.

In a second phase a multiscale mechanistic description of ultrahigh dose rate induced damage including oxygen interplay and reactive oxygen species production and reactions will be developed. Our approach is based on chemical track structure Monte Carlo simulations and dedicated extensions of analytical biophysical models.

Results

We expect to obtain:

-Real time dosimetric methods to monitor FLASH beams for cells and mice irradiations. The same methods can be also translated to monitor FLASH delivery to human patients.

-A refined mechanistic description of the FLASH effect starting from basic radiation chemistry concepts in a biological environment. We will also provide in vitro and in vivo validation tests using two types of FLASH beams.

Conclusions

This work will contribute to unraveling the basic biological mechanisms of the FLASH effect and, at the same time, it will provide accurate real time dosimetric tools not available at the moment.