Expanding dose and dose‐rate capabilities of a synchrotron‐based pre‐clinical proton FLASH irradiation platform

Abstract Background Proton FLASH radiotherapy has demonstrated promising normal tissue sparing for similar tumor control at ultra‐high dose rates (> 40 Gy/s), but systematic investigation of dose‐rate‐dependent biological mechanisms is limited. Most existing proton platforms operate within a narrow dose‐rate range. Synchrotron‐based systems are further constrained by limited beam current and cyclic (“spill‐based”) delivery. Purpose To develop and validate a synchrotron‐based small‐animal proton irradiation platform with expanded and controllable dose and dose‐rate capabilities, enabling systematic studies across conventional, intermediate (meso)‐dose‐rate (μDR: 1–40 Gy/s) and FLASH regimes. Methods The beamline was redesigned to incorporate three beam modulation modes (low, mid, and high dose) by modifying initial scattering conditions and re‐optimizing and repositioning downstream components, including cone‐shaped flattening filters, ridge filters, and range compensators. 14 discrete synchrotron beam extraction settings (denoted as “IDs”) with different beam fluxes were developed and combined with 3 beam modulation modes, resulting in 42 dose and dose‐rate combinations. Ridge filters were fabricated using resin‐based 3D printing with an iterative geometric correction workflow. Depth‐dose distributions were measured using an Advanced Markus ionization chamber, and lateral dose profiles were verified using radiochromic film. Results The low‐, mid‐, and high‐dose modes achieved maximum single‐spill doses of 20.8 Gy (205 Gy/s), 30.2 Gy (297 Gy/s), and 53.8 Gy (531 Gy/s), respectively. Across all beam IDs and modulation modes, dose rates ranged from approximately 13 Gy/s to 2200 Gy/s, spanning μDR and FLASH regimes. Measured depth‐dose profiles agreed with Monte Carlo simulations within ± 4%, and lateral dose flatness was within ± 3.7%. Conclusions This modular beamline redesign significantly expands the achievable dose and dose‐rate combinations of a synchrotron‐based proton irradiation platform without requiring accelerator modifications. The system enables 42 reproducible dose and dose‐rate configurations with single‐spill delivery, providing a flexible framework for systematic investigation of dose‐rate‐dependent radiobiological proton FLASH effects.