Laser-FLASH: radiobiology at high dose, ultra-high dose-rate, single pulse laser-driven proton source

TL;DR

This paper demonstrates the use of ultra-high dose-rate laser-driven proton sources to deliver single nanosecond pulses of radiation, enabling novel radiobiological studies within the FLASH irradiation protocol.

Contribution

It introduces a method for single-pulse, high-dose irradiation using laser-driven protons, with a new dosimetry protocol and initial biological results.

Findings

Reduced oxidative stress in vitro

Decreased developmental damage in vivo

Confirmed anti-tumoral efficacy

Abstract

Laser-driven proton sources have long been developed with an eye on their potential for medical application to radiation therapy. These sources are compact, versatile, and show peculiar characteristics such as extreme instantaneous dose rates, short duration and broad energy spectrum. Typical temporal modality of laser-driven irradiation, the so-called fast-fractionation, results from the composition of multiple, temporally separated, ultra-short dose fractions. In this paper we present the use of a high-energy laser system for delivering the target dose in a single nanosecond pulse, for ultra-fast irradiation of biological samples. A transport line composed by two permanent magnet quadrupoles and a scattering system is used to improve the dose profile and to control the delivered dose-per-pulse. A single-shot dosimetry protocol for the broad-spectrum proton source using Monte Carlo simulations was developed. Doses as high as 20Gy could be delivered in a single shot, lasting less than 10ns over a 1.0cm diameter sample holder, at a dose-rate exceeding 10^9 Gy/s. Exploratory application of extreme laser-driven irradiation conditions, falling within the FLASH irradiation protocol, are presented for in vitro and in vivo irradiation. A reduction of radiation-induced oxidative stress in-vitro and radiation-induced developmental damage in vivo were observed, whereas anti-tumoral efficacy was confirmed by cell survival assay.