A new platform for ultra-high dose rate radiobiological research using the BELLA PW laser proton beamline

Abstract

Radiotherapy is the current standard of care for more than 50% of all cancer patients. Improvements in radiotherapy (RT) technology have increased tumor targeting and normal tissue sparing. Radiations at ultra-high dose rates required for FLASH-RT effects have sparked interest in potentially providing additional differential therapeutic benefits. We present a new experimental platform that is the first one to deliver petawatt laser-driven proton pulses of 2 MeV energy at 0.2 Hz repetition rate by means of a compact, tunable active plasma lens beamline to biological samples. Cell monolayers grown over a 10 mm diameter field were exposed to clinically relevant proton doses ranging from 7 to 35 Gy at ultra-high instantaneous dose rates of 107 Gy/s. Dose-dependent cell survival measurements of human normal and tumor cells exposed to LD protons showed significantly higher cell survival of normal-cells compared to tumor-cells for total doses of 7 Gy and higher, which was not observed to the same extent for X-ray reference irradiations at clinical dose rates. These findings provide preliminary evidence that compact LD proton sources enable a new and promising platform for investigating the physical, chemical and biological mechanisms underlying the FLASH effect.

Online Charge Measurement for Petawatt Laser-Driven Ion Acceleration

“…The cell samples were located in air at 1.7 m downstream from the point of laser-target interaction. A portion of the TNSA ion beam was captured and transported downstream by an active plasma lens (APL) on a remote controlled hexapod [11,23]. The APL consisted of a 33 mm long capillary filled with argon gas at a pressure of 5 Torr inside the channel of 1 mm diameter.…”

“…At the current uncertainty associated with the model function for D(Q), (∆D/D) SSF could be lowered to ∼ 0.11 for total doses >2.5 Gy and even to < 0.1 for doses >10 Gy. It should be pointed out that the relative dose uncertainty resulting from lateral dose variations across the cell samples was 0.19 [11] and will also need to be reduced in the future to improve the overall irradiation precision, however, those efforts are beyond the scope of this paper.…”

“…In an experiment conducted at the Berkeley Lab Laser Accelerator (BELLA) petawatt (PW) laser facility that was described in Ref. [11], biological cells were irradiated with LD protons at an instantaneous dose rate of 10 7 Gy/s up to a total absorbed dose of > 30 Gy by accumulating shots at 0.2 Hz repetition rate. After irradiation, the surviving fractions of normal human prostate and prostate tumor cells were compared and it was demonstrated for the first time that LD protons delivered at ultra-high IDR can indeed induce the differential sparing of normal versus tumor cells in vitro for total doses ≥ 7 Gy [11].…”

“…Here we present an alternative, fully non-invasive method for online charge measurements of LD ion beams in the form of an integrating current transformer (ICT). To that end an ICT (Bergoz Instrumentation), which had been previously used to measure LD electron bunches generated at the BELLA Center [17,18], was now characterized for the first time during biological cell sample irradiations with few MeV LD protons at the BELLA PW beamline described in [11].…”

Snowmass 2021 Accelerator Frontier White Paper: Near Term Applications driven by Advanced Accelerator Concepts

“…With the biological mechanisms underlying the FLASH effect remaining largely unknown, research into the radiobiological effects of ultra-high dose rate proton irradiation has been hampered by limited access to conventional accelerators that are able to provide the required dose rates [97,98]. In a preliminary study at the 40 Joule BELLA petawatt laser proton beamline, it was demonstrated for the first time that LD protons delivered at ultra-high IDR can indeed induce the differential sparing of normal versus tumor cells in vitro for total doses ≥ 7 Gy [80]. In that study, normal and tumor prostate cells in 1 cm diameter cups were irradiation with LD protons of 2-8 MeV at an IDR of 10 7 Gy/s.…”