Tumour irradiation in mice with a laser-accelerated proton beam

Florian Kroll,Kerstin Brüchner,Uwe Helbig,René Gebhardt,Jörg Pawelke,Thomas Püschel,Umar Masood,Elisabeth Bodenstein,Josefine Metzkes-Ng,U Schramm ,T Kluge ,Lennart Gaus,Christian Richter,Alexej Nossula,Florian‐Emanuel Brack ,Jens Pietzsch,Hans-Peter Schlenvoigt,Sebastian Meister,Constantin Bernert,Karl Zeil,Mechthild Krause,Tim Ziegler,Martin Rehwald,Stefan Bock,Stephan Kraft,Elisabeth Leßmann ,T E Cowan ,Marvin Elias Paul Umlandt ,Marvin Reimold,L Karsch ,Elke Beyreuther

doi:10.1038/s41567-022-01520-3

Abstract

Recent oncological studies identified beneficial properties of radiation applied at ultrahigh dose rates, several orders of magnitude higher than the clinical standard of the order of Gy min–1. Sources capable of providing these ultrahigh dose rates are under investigation. Here we show that a stable, compact laser-driven proton source with energies greater than 60 MeV enables radiobiological in vivo studies. We performed a pilot irradiation study on human tumours in a mouse model, showing the concerted preparation of mice and laser accelerator, dose-controlled, tumour-conform irradiation using a laser-driven as well as a clinical reference proton source, and the radiobiological evaluation of irradiated and unirradiated mice for radiation-induced tumour growth delay. The prescribed homogeneous dose of 4 Gy was precisely delivered at the laser-driven source. The results demonstrate a complete laser-driven proton research platform for diverse user-specific small animal models, able to deliver tunable single-shot doses up to around 20 Gy to millimetre-scale volumes on nanosecond timescales, equivalent to around 109 Gy s–1, spatially homogenized and tailored to the sample. The platform provides a unique infrastructure for translational research with protons at ultrahigh dose rates.

Highlights

Since the beginning of external beam radiotherapy (RT), accelerator research and development has constantly advanced RT technology for the treatment of cancer patients[1]
We investigate how proton sources based on laser–plasma acceleration (LPA) can fill this gap
Advancing a laser–plasma research setup to the performance, instrumentation, readiness and stability level required for high-level interdisciplinary irradiation studies, on living samples, poses a major hurdle to be cleared for LPA sources[26]

Summary

Introduction

Since the beginning of external beam radiotherapy (RT), accelerator research and development has constantly advanced RT technology for the treatment of cancer patients[1]. The observed radiation-induced tumour growth delay in a mouse model (sample size, 92 animals), examined at a single-dose point ((4.0 ± 0.4) Gy), proves the achievement of the unique interplay of long-term stable proton LPA-source operation at the highest performance and precise dose delivery and dosimetry adapted to the ultrahigh bunch dose rate at millimetre-scale irradiation fields with the complex requirements of a radiobiological study.

Results

Conclusion