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arxiv: 2605.05441 · v1 · submitted 2026-05-06 · ⚛️ physics.med-ph · physics.acc-ph· physics.ins-det

Recognition: unknown

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

Alexander Gottstein, Cristian Fernandez Palomo, Eva Kasanda, Gaia Dellepiane, Isidre Mateu, Jan Gruber, Lars Eggiman, Maria Vittoria Rossi, Paola Scampoli, Paolo Pellicioli, Pierluigi Casolaro, Saverio Braccini, Thierry Stammbach

Authors on Pith no claims yet

Pith reviewed 2026-05-08 15:33 UTC · model grok-4.3

classification ⚛️ physics.med-ph physics.acc-phphysics.ins-det
keywords proton radiobiologyFLASH irradiationminibeamspatially fractionated radiotherapymedical cyclotrondosimetrybeamline adaptationpre-clinical studies
0
0 comments X

The pith

The 18 MeV Bern Medical Cyclotron beamline has been adapted to deliver protons across conventional to FLASH dose rates and minibeam patterns for pre-clinical radiobiology.

A machine-rendered reading of the paper's core claim, the machinery that carries it, and where it could break.

The paper reports the modification of the cyclotron's beam transfer line using collimators, scattering foils, and drift space to create controllable irradiation fields at 18 MeV. A dosimetry setup combining an ionization chamber with radiochromic film that includes linear energy transfer corrections was used to quantify doses in cell flasks. The resulting system produces stable beams from 0.01 to 100 Gy/s with uniformity under 8 percent inside a 20 mm radius and supports spatially fractionated grids at practical distances. A sympathetic reader would care because the work turns an existing medical isotope cyclotron into a research tool that lets biologists test how dose rate and beam microstructure alter cellular responses without requiring new high-energy accelerators.

Core claim

The adapted 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 percent. 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 of 15.54 MeV extracted into air facilitates compact SFRT implementation with well-resolved minibeams.

What carries the argument

The adapted Beam Transfer Line with passive shaping via collimators, scattering foils, and extended drift space together with an in-beam ionization chamber and LET-corrected radiochromic film dosimetry.

If this is right

  • Systematic pre-clinical proton radiobiology studies become feasible under controlled variations of dose rate and spatial delivery.
  • Optimization of proton FLASH and spatially fractionated radiotherapy parameters can proceed on an accessible platform.
  • Accelerator technology is linked to radiobiology through a flexible, existing medical cyclotron without new dedicated infrastructure.

Where Pith is reading between the lines

These are editorial extensions of the paper, not claims the author makes directly.

  • The same passive-shaping approach could be replicated on other radionuclide cyclotrons to create low-cost research beamlines at similar energies.
  • Standardized LET-corrected film dosimetry at these energies may improve reproducibility of low-energy proton experiments across different laboratories.
  • Biological data collected on this platform could inform the minimum beam energy and dose-rate requirements needed for clinical proton FLASH systems.

Load-bearing premise

The LET-dependent corrections on radiochromic film yield accurate quantitative dose values in cell-culture flasks and the reported uniformity and stability are adequate for reliable biological experiments.

What would settle it

A side-by-side comparison in which film doses measured in a flask geometry, after LET correction, deviate by more than 10 percent from independent ionization-chamber readings at the same position.

read the original 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{\mu A}$. 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.

Editorial analysis

A structured set of objections, weighed in public.

Desk editor's note, referee report, simulated authors' rebuttal, and a circularity audit. Tearing a paper down is the easy half of reading it; the pith above is the substance, this is the friction.

Referee Report

1 major / 1 minor

Summary. The paper describes the adaptation of the Beam Transfer Line (BTL) of the 18 MeV Bern Medical Cyclotron (BMC) for pre-clinical proton radiobiology research, adding FLASH and proton minibeam (SFRT) capabilities. Passive beam shaping via collimators, scattering foils, and drift space is used to produce irradiation fields. A dosimetric framework employs an in-beam ionization chamber and radiochromic film with LET-dependent corrections. Reported results include dose uniformity below 8% within a 20 mm radius, dose rates spanning 0.01–100 Gy/s, and extracted beam energies of 15.54(12) MeV in air and 8.14(28) MeV at the target (cell flask) position. The work positions the adapted BMC as a flexible platform for systematic studies of proton FLASH and SFRT.

Significance. If the dosimetry is shown to be quantitatively accurate, the platform would provide an accessible, low-energy proton source for controlled pre-clinical experiments varying dose rate and spatial fractionation. This could help optimize emerging modalities like proton FLASH and SFRT and strengthen links between accelerator technology and radiobiology.

major comments (1)
  1. [Abstract and dosimetric framework] Abstract and dosimetric framework description: The central claim that the beamline enables quantitative and accurate dose delivery for in-vitro radiobiology under conventional and FLASH regimes rests on the LET-dependent radiochromic film corrections. The manuscript states that these corrections are necessary and that quantitative dosimetry is achievable, yet provides no calibration procedure, assumed LET spectrum, or cross-check against an energy-independent primary standard (e.g., Faraday cup or water calorimeter) at the 8.14(28) MeV target position. At this degraded energy the LET gradient is steep; any mismatch would directly affect reported dose rates, uniformity, and SFRT profiles, limiting biological interpretability. Validation data or a supplementary methods section addressing this is required.
minor comments (1)
  1. [Results and methods] The abstract and results summary report concrete values (uniformity <8%, energies with uncertainties, dose-rate range) but the manuscript lacks accompanying data tables, error budgets, or full experimental methods, which would improve reproducibility and allow independent assessment of the measurements.

Simulated Author's Rebuttal

1 responses · 0 unresolved

We thank the referee for their constructive feedback on our manuscript. The comment highlights an important aspect of the dosimetric framework that requires clarification and additional detail. We address it point by point below and have prepared revisions to strengthen the presentation of our methods.

read point-by-point responses

  1. Referee: [Abstract and dosimetric framework] Abstract and dosimetric framework description: The central claim that the beamline enables quantitative and accurate dose delivery for in-vitro radiobiology under conventional and FLASH regimes rests on the LET-dependent radiochromic film corrections. The manuscript states that these corrections are necessary and that quantitative dosimetry is achievable, yet provides no calibration procedure, assumed LET spectrum, or cross-check against an energy-independent primary standard (e.g., Faraday cup or water calorimeter) at the 8.14(28) MeV target position. At this degraded energy the LET gradient is steep; any mismatch would directly affect reported dose rates, uniformity, and SFRT profiles, limiting biological interpretability. Validation data or a supplementary methods section addressing this is required.

    Authors: We agree that the current manuscript lacks sufficient detail on the LET-dependent corrections to fully substantiate the claim of quantitative dosimetry. The radiochromic film (EBT3) measurements were performed with corrections derived from published stopping-power data for protons at energies around 8 MeV, using the beam energy degradation calculated via Monte Carlo simulations of the beamline components. However, the manuscript does not explicitly describe the calibration procedure, the specific LET spectrum assumed at the cell-flask position, or direct cross-validation against a primary standard. In the revised manuscript we will add a dedicated Supplementary Methods section that (i) details the film calibration protocol, including the assumed LET values and the correction factors applied, (ii) presents the comparison between ionization-chamber and film readings at the target position, and (iii) quantifies the associated uncertainties arising from the LET gradient. A Faraday-cup or water-calorimeter cross-check was not feasible within the existing beamline geometry, but the in-beam ionization chamber was calibrated against a secondary standard traceable to a national metrology institute. These additions will directly address the referee’s concern and improve the interpretability of the reported dose rates and uniformity figures. revision: yes

Circularity Check

0 steps flagged

No circularity: purely experimental hardware and dosimetry paper with direct observations only

full rationale

The paper reports adaptation of an existing cyclotron beamline, passive beam shaping, and measurements of uniformity, dose rates, and profiles using ionization chambers and radiochromic film. No mathematical derivations, fitted models, predictions from parameters, or self-referential claims appear in the abstract or described content. Results are presented as measured outcomes (e.g., uniformity <8%, dose rates to 100 Gy/s, energy degradation to 8.14 MeV). The LET-dependent film corrections are described as implemented and necessary based on observations, without any reduction to self-defined inputs or self-citations that bear the central claim. This matches the default expectation for non-circular experimental reports.

Axiom & Free-Parameter Ledger

0 free parameters · 1 axioms · 0 invented entities

The central claim rests on experimental beam shaping and dosimetry measurements rather than theoretical derivations. No free parameters, new axioms, or invented entities are introduced in the abstract.

axioms (1)
  • standard math Standard assumptions of proton beam transport, scattering, and energy loss in matter apply to the collimators, foils, and drift space.
    Invoked implicitly for passive beam shaping and energy degradation to 8.14 MeV at target.

pith-pipeline@v0.9.0 · 5684 in / 1455 out tokens · 95176 ms · 2026-05-08T15:33:43.461265+00:00 · methodology

discussion (0)

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Reference graph

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