“Broadbeam” irradiation of mammalian cells using a vertical microbeam facility

Jeynes, Jonathan C. G.; Merchant, Michael J; Barazzuol, Lara; Barry, M; Guest, Derek; Palitsin, Vladimir; Grime, G.W.; Tullis, Iain D. C.; Barber, Paul R.; Vojnovic, B.; Kirkby, K.J.

doi:10.1007/s00411-013-0487-4

Cited by 16 publications

(11 citation statements)

References 28 publications

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“…The LET of the ion determines the dose it imparts, consequently cells are irradiated with a far greater number of low-LET ions for the same equivalent dose of high-LET particles (Jeynes et al, 2013b). Therefore the probability of an ion hitting a vesicle containing nanoparticles is greater with higher energy, low-LET protons, as there are more ions traversing the cell.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were irradiated using a 2 MV Tandetron TM High Voltage accelerator at the University of Surrey's Ion Beam Centre. The vertical beamline (Merchant et al 2012) was used, with a procedure which has been described previously (Jeynes et al 2013b). Here, the cells are pipetted onto a polypropylene-bottomed dish in a 15 µl droplet and left for 10 min for the cells to settle on the bottom of the dish.…”

Section: Proton Irradiationmentioning

confidence: 99%

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Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

et al. 2014

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Gold nanoparticles (GNPs) have been shown to sensitise cancer cells to X-ray radiation, particularly at kV energies where photoelectric interactions dominate and the high atomic number of gold makes a large difference to X-ray absorption. Protons have a high cross-section for gold at a large range of relevant clinical energies, and so potentially could be used with GNPs for increased therapeutic effect.Here, we investigate the contribution of secondary electron emission to cancer cell radiosensitisation and investigate how this parameter is affected by proton energy and a free radical scavenger. We simulate the emission from a realistic cell phantom containing GNPs after traversal by protons and X-rays with different energies. We find that with a range of proton energies (1 -250 MeV) there is a small increase in secondaries compared to a much larger increase with X-rays. Secondary electrons are known to produce toxic free radicals. Using a cancer cell line in vitro we find that a free radical scavenger has no protective effect on cells containing GNPs irradiated with 3 MeV protons, while it does protect against cells irradiated with X-rays.3

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Section: Discussionmentioning

confidence: 99%

Section: Proton Irradiationmentioning

confidence: 99%

Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

et al. 2014

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“…(2) were used in this study. The obtained dataset includes 267 data points from 34 publications (Aoki et al, 2000, Belli et al, 1998, Belli et al, 2008, Bird and Burki, 1975, Blomquist et al, 1993, Böhrnsen et al, 1993, Britten et al, 2013, Cox et al, 1977ab, Doria et al, 2012, Folkard et al, 1989, Folkard et al, 1996, Furusawa et al, 2000, Furusawa et al, 2002, Gerelchuluun et al, 2015, Hall et al, 1972, Hall et al, 1977, Hirayama et al, 2009, Jenner et al, 1993, Jeynes et al, 2013, Perris et al, 1986, Prise et al, 1990, Raju et al, 1991, Scholz, 2003, Schuff et al, 2002, Stenerlöw et al, 1995, Thacker et al, 1979, Tilly, 1999, Weber and Flentje, 1993, Wouters et al, 1996, Wouters et al, 2015, Wulf et al, 1985, Zhou et al, 2006 approximately 1 to 15000 keV/µm. Each data point is composed by the following quantities: the primary-beam unrestricted dose-mean LET (𝐿𝐸𝑇 ), the linear and the quadratic terms of the survival curve fitted using the linear quadratic model (McMahon, 2018) in case of ion exposure (respectively 𝛼 and 𝛽) and for the reference photon exposure (𝛼 and 𝛽 ).…”

Section: 𝐿𝐸𝑇 = ∫ 𝐿𝐸𝑇 𝑑(𝐿𝐸𝑇) D𝐿𝐸𝑇mentioning

confidence: 99%

Development of a new microdosimetric biological weighting function for the RBE₁₀ assessment in case of the V79 cell line exposed to ions from ¹H to ²³⁸U

Parisi¹,

Sato²,

Matsuya³

et al. 2020

Phys. Med. Biol.

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An improved biological weighting function (IBWF) is proposed to phenomenologically relate microdosimetric lineal energy probability density distributions with the relative biological effectiveness (RBE) for the in vitro clonogenic cell survival (surviving fraction = 10%) of the most commonly used mammalian cell line, i.e. the Chinese hamster lung fibroblasts (V79). The IBWF, intended as a simple and robust tool for a fast RBE assessment to compare different exposure conditions in particle therapy beams, was determined through an iterative global-fitting process aimed to minimize the average relative deviation between RBE calculations and literature in vitro data in case of exposure to various types of ions from 1H to 238U. By using a single particle- and energy- independent function, it was possible to establish an univocal correlation between lineal energy and clonogenic cell survival for particles spanning over an unrestricted linear energy transfer range of almost five orders of magnitude (0.2 keV µm−1 to 15 000 keV µm−1 in liquid water). The average deviation between IBWF-derived RBE values and the published in vitro data was ∼14%. The IBWF results were also compared with corresponding calculations (in vitro RBE10 for the V79 cell line) performed using the modified microdosimetric kinetic model (modified MKM). Furthermore, RBE values computed with the reference biological weighting function (BWF) for the in vivo early intestine tolerance in mice were included for comparison and to further explore potential correlations between the BWF results and the in vitro RBE as reported in previous studies. The results suggest that the modified MKM possess limitations in reproducing the experimental in vitro RBE10 for the V79 cell line in case of ions heavier than 20Ne. Furthermore, due to the different modelled endpoint, marked deviations were found between the RBE values assessed using the reference BWF and the IBWF for ions heavier than 2H. Finally, the IBWF was unchangingly applied to calculate RBE values by processing lineal energy density distributions experimentally measured with eight different microdosimeters in 19 1H and 12C beams at ten different facilities (eight clinical and two research ones). Despite the differences between the detectors, irradiation facilities, beam profiles (pristine or spread out Bragg peak), maximum beam energy, beam delivery (passive or active scanning), energy degradation system (water, PMMA, polyamide or low-density polyethylene), the obtained IBWF-based RBE trends were found to be in good agreement with the corresponding ones in case of computer-simulated microdosimetric spectra (average relative deviation equal to 0.8% and 5.7% for 1H and 12C ions respectively).

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“…The Wolfson Surrey vertical microbeam (WSVM) was used in this research as a facility that provides highly focused high-LET radiation. A complete description of this microbeam can be found in Merchant et al ( 30 ) and Jeynes et al ( 31 ). Therefore, only a short overview will follow.…”

Section: Clonogenic Survival Assay Using High-let Microbeam Irradiatimentioning

confidence: 99%

Applications of High-Throughput Clonogenic Survival Assays in High-LET Particle Microbeams

et al. 2016

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Charged particle therapy is increasingly becoming a valuable tool in cancer treatment, mainly due to the favorable interaction of particle radiation with matter. Its application is still limited due, in part, to lack of data regarding the radiosensitivity of certain cell lines to this radiation type, especially to high-linear energy transfer (LET) particles. From the earliest days of radiation biology, the clonogenic survival assay has been used to provide radiation response data. This method produces reliable data but it is not optimized for high-throughput microbeam studies with high-LET radiation where high levels of cell killing lead to a very low probability of maintaining cells’ clonogenic potential. A new method, therefore, is proposed in this paper, which could potentially allow these experiments to be conducted in a high-throughput fashion. Cells are seeded in special polypropylene dishes and bright-field illumination provides cell visualization. Digital images are obtained and cell detection is applied based on corner detection, generating individual cell targets as x–y points. These points in the dish are then irradiated individually by a micron field size high-LET microbeam. Post-irradiation, time-lapse imaging follows cells’ response. All irradiated cells are tracked by linking trajectories in all time-frames, based on finding their nearest position. Cell divisions are detected based on cell appearance and individual cell temporary corner density. The number of divisions anticipated is low due to the high probability of cell killing from high-LET irradiation. Survival curves are produced based on cell’s capacity to divide at least four to five times. The process is repeated for a range of doses of radiation. Validation shows the efficiency of the proposed cell detection and tracking method in finding cell divisions.

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“Broadbeam” irradiation of mammalian cells using a vertical microbeam facility

Cited by 16 publications

References 28 publications

Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

Development of a new microdosimetric biological weighting function for the RBE₁₀ assessment in case of the V79 cell line exposed to ions from ¹H to ²³⁸U

Applications of High-Throughput Clonogenic Survival Assays in High-LET Particle Microbeams

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“Broadbeam” irradiation of mammalian cells using a vertical microbeam facility

Cited by 16 publications

References 28 publications

Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

Development of a new microdosimetric biological weighting function for the RBE10 assessment in case of the V79 cell line exposed to ions from 1H to 238U

Applications of High-Throughput Clonogenic Survival Assays in High-LET Particle Microbeams

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Development of a new microdosimetric biological weighting function for the RBE₁₀ assessment in case of the V79 cell line exposed to ions from ¹H to ²³⁸U