Development of a Proton Therapy Research Beamline with FLASH and Minibeam Capabilities at the 18 MeV Bern Medical Cyclotron

Abstract: Advanced radiotherapy approaches such as FLASH irradiation and spatially fractionated radiotherapy (SFRT) show potential to improve the therapeutic ratio, yet their biological mechanisms and optimal delivery parameters remain uncertain. Progress requires accessible proton research platforms with flexible temporal and spatial dose delivery. We report on the adaptation of the Beam Transfer Line (BTL) of the Bern Medical Cyclotron (BMC) for radiobiology research with FLASH and proton minibeam capabilities. The BMC is optimized for the production of radionuclides for medical imaging, and is able to extract currents up to 150 $ \mathrm{μA}$. The 18 MeV proton beam was passively shaped using collimators, scattering foils, and extended drift space to generate irradiation fields. A dosimetric framework was implemented using an in-beam ionization chamber and radiochromic film with LET-dependent corrections. Beam uniformity and SFRT profiles with various grid spacings were evaluated at realistic target distances. The developed beamline enables stable delivery under controlled conditions in both conventional and FLASH regimes, spanning dose rates from 0.01 to 100 Gy/s. Dose uniformity within a 20 mm radius was below 8\%. Film measurements confirmed the need for LET-dependent corrections and indicated that quantitative dosimetry in in-vitro setups is achievable with appropriate LET corrections. The low proton energy (15.54(12) MeV extracted into air, 8.14(28) MeV delivered to cells in flask) facilitates compact SFRT implementation with well-resolved minibeams. The adapted BMC provides a flexible and accessible platform for systematic pre-clinical proton radiobiology studies under varied dose-rate and spatial delivery conditions. This supports optimization of emerging modalities such as proton FLASH and SFRT and helps bridge accelerator technology and radiobiology.