Abstract
BackgroundHigh-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.AimTo develop an in vitro approach to determine biological dose equivalence between MRT and BB using two different cell-based assays.MethodsThe 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.ResultsFor 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.ConclusionOur 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.
Highlights
Our data provides the first determination of biological dose equivalence between BB and microbeam radiation therapy (MRT) modalities for different cell lines and identifies real time cell impedance sensing (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
Synchrotron microbeam radiation therapy (MRT) is an experimental form of radiation therapy in which synchrotrongenerated X-rays are segmented by a collimator, producing intense microbeams, tens of mm wide separated by hundreds of mm
Summary
Synchrotron microbeam radiation therapy (MRT) is an experimental form of radiation therapy in which synchrotrongenerated X-rays are segmented by a collimator, producing intense microbeams, tens of mm wide separated by hundreds of mm. Synchrotron MRT has been used to ablate tumours in animal models at radiation levels that spare normal tissues [1,2,3,4,5,6,7,8], with an apparent increase in the therapeutic index of up to 5-fold over conventional/broadbeam (BB) radiotherapy [1,4]. One of the major hurdles to implementation of MRT as a therapeutic option for cancer is to identify the optimal radiation dose to treat different tumours. 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
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