title: An evaluation of dose equivalence between synchrotron microbeam radiation therapy and conventional broad beam radiation using clonogenic and cell impedance assays.
abstract: BACKGROUND
  High-dose synchrotron microbeam radiation therapy (MRT) has shown the potential to deliver improved outcomes over conventional broadbeam (BB) radiation therapy. To implement synchrotron MRT clinically for cancer treatment, it is necessary to undertake dose equivalence studies to identify MRT doses that give similar outcomes to BB treatments.
  
  
  OBJECTIVE
  To develop an in vitro approach to determine biological dose equivalence between MRT and BB using two different cell-based assays.
  
  
  METHODS
  The acute response of tumour and normal cell lines (EMT6.5, 4T1.2, NMuMG, EMT6.5ch, 4T1ch5, SaOS-2) to MRT (50-560 Gy) and BB (1.5-10 Gy) irradiation was investigated using clonogenic and real time cell impedance sensing (RT-CIS)/xCELLigence assays. MRT was performed using a lattice of 25 or 50 µm-wide planar, polychromatic kilovoltage X-ray microbeams with 200 µm peak separation. BB irradiations were performed using a Co60 teletherapy unit or a synchrotron radiation source. BB doses that would generate biological responses similar to MRT were calculated by data interpolation and verified by clonogenic and RT-CIS assays.
  
  
  RESULTS
  For a given cell line, MRT equivalent BB doses identified by RT-CIS/xCELLigence were similar to those identified by clonogenic assays. Dose equivalence between MRT and BB were verified in vitro in two cell lines; EMT6.5ch and SaOS-2 by clonogenic assays and RT-CIS/xCELLigence. We found for example, that BB doses of 3.4±0.1 Gy and 4.40±0.04 Gy were radiobiologically equivalent to a peak, microbeam dose of 112 Gy using clonogenic and RT-CIS assays respectively on EMT6.5ch cells.
  
  
  CONCLUSIONS
  Our data provides the first determination of biological dose equivalence between BB and MRT modalities for different cell lines and identifies RT-CIS/xCELLigence assays as a suitable substitute for clonogenic assays. These results will be useful for the safe selection of MRT doses for future veterinary and clinical trials.
authors.affiliation: Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia; Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia.
authors.forename: Mohammad Johari
authors.initials: MJ
authors.lastname: Ibahim
authors.affiliation: Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia; William Buckland Radiotherapy Centre, Alfred Hospital, Melbourne, Australia.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Crosbie
authors.affiliation: Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Marina
authors.initials: M
authors.lastname: Zaitseva
authors.affiliation: Australian Synchrotron Imaging and Medical Beamline, Clayton, Australia; CSIRO Materials Science & Engineering, Clayton, Australia.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Stevenson
authors.affiliation: Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Peter A W
authors.initials: PA
authors.lastname: Rogers
authors.affiliation: Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Premila
authors.initials: P
authors.lastname: Paiva
mesh_terms: D000818:Animals; D001315:Australia; D001681:Biological Assay / Q000379:methods*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002999:Clone Cells; D004307:Dose-Response Relationship, Radiation; D017097:Electric Impedance; D051379:Mice; D017356:Synchrotrons; D013810:Therapeutic Equivalency