title: Development of a facility for high-precision irradiation of cells with carbon ions.
abstract: OBJECTIVE
  Compared to photons, using particle radiation in radiotherapy reduces the dose and irradiated volume of normal tissues, potentially reducing side effects. The biological effect of dose deposited by particles such as carbon ions, however, differs from that of dose deposited by photons. The inaccuracy in models to estimate the biological effects of particle radiation remains the most important source of uncertainties in particle therapy. Improving this requires high-precision studies on biological effects of particle radiation. Therefore, the authors aimed to develop a facility for reproducible and high-precision carbon-ion irradiation of cells in culture. The combined dose nonuniformity in the lateral and longitudinal direction should not exceed +/-1.5%. Dose to the cells from particles than other carbon ions should not exceed 5%.
  
  
  METHODS
  A uniform lateral dose distribution was realized using a single scatter foil and quadrupole magnets. A modulator wheel was used to create a uniform longitudinal dose distribution. The choice of beam energy and the optimal design of these components was determined using GEANT4 and SRIM Monte Carlo simulations. Verification of the uniformity of the dose distribution was performed using a scintillating screen (lateral) and a water phantom (longitudinal). The reproducibility of dose delivery between experiments was assessed by repeated measurements of the spatial dose distribution. Moreover, the reproducibility of dose-response measurements was tested by measuring the survival of irradiated HEK293 cells in three independent experiments.
  
  
  RESULTS
  The relative contribution of dose from nuclear reaction fragments to the sample was found to be <5% when using 90 MeV/u carbon ions. This energy still allows accurate dosimetry conforming to the IAEA Report TRS-398, facilitating comparison to dose-effect data obtained with other radiation qualities. A 1.3 mm long spread-out Bragg peak with a diameter of 30 mm was created, allowing the irradiation of cell samples with the specified accuracy. Measurements of the transverse and longitudinal dose distribution showed that the dose variation over the sample volume was +/-0.8% and +/-0.7% in the lateral and longitudinal directions, respectively. The track-averaged LET of 132 +/- 10 keV/microm and dose-averaged LET of 189 +/- 15 keV/microm at the position of the sample were obtained from a GEANT4 simulation, which was validated experimentally. Three separately measured cell-survival curves yielded nearly identical results.
  
  
  CONCLUSIONS
  With the new facility, high-precision carbon-ion irradiations of biological samples can be performed with highly reproducible results.
authors.affiliation: Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713AV Groningen, The Netherlands.
authors.forename: Marc-Jan
authors.initials: MJ
authors.lastname: van Goethem
authors.forename: Maarten
authors.initials: M
authors.lastname: Niemantsverdriet
authors.forename: Sytze
authors.initials: S
authors.lastname: Brandenburg
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.forename: Robert P
authors.initials: RP
authors.lastname: Coppes
authors.forename: Peter
authors.initials: P
authors.lastname: van Luijk
mesh_terms: D002244:Carbon / Q000737:chemistry / Q000627:therapeutic use*; D002470:Cell Survival / Q000528:radiation effects; D002477:Cells / Q000473:pathology / Q000528:radiation effects*; D057809:HEK293 Cells; D006801:Humans; D018499:Linear Energy Transfer; D011874:Radiometry; D011878:Radiotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D015203:Reproducibility of Results
chemical_list: D002244:Carbon