Kiyoshi Yasuoka

Induction of in situ DNA double-strand breaks and apoptosis by 200 MeV protons and 10 MV X-rays in human tumour cell lines

Purpose:u2003To clarify the properties of clinical high-energy protons by comparing with clinical high-energy X-rays. Materials and methods:u2003Human tumor cell lines, ONS76 and MOLT4, were irradiated with 200 MeV protons or 10 MV X-rays. In situ DNA double-strand breaks (DDSB) induction was evaluated by immunocytochemical staining of phosphorylated histone H2AX (γ-H2AX). Apoptosis was measured by flow-cytometry after staining with Annexin V. The relative biological effectiveness (RBE) was obtained by clonogenic survival assay. Results:u2003DDSB induction was significantly higher for protons than X-rays with average ratios of 1.28 (ONS76) and 1.59 (MOLT4) at 30u2009min after irradiation. However the differences became insignificant at 6u2009h. Also, apoptosis induction in MOLT4 cells was significantly higher for protons than X-rays with an average ratio of 2.13 at 12u2009h. However, the difference became insignificant at 20u2009h. RBE values of protons to X-rays at 10% survival were 1.06u200a±u200a0.04 and 1.02u200a±u200a0.15 for ONS76 and MOLT4, respectively. Conclusions:u2003Cell inactivation may differ according to different timings and/or endpoints. Proton beams demonstrated higher cell inactivation than X-rays in the early phases. These data may facilitate the understanding of the biological properties of clinical proton beams.

Study on the use of electron-tracking Compton gamma-ray camera to monitor the therapeutic proton dose distribution in real time

Radiation therapy with proton and heavy-ion beams has been better established lately and the patient throughput is increasing. Although the therapy beam is controlled with high accuracy, it is difficult to know the location of distal dose falloff in the body. If real-time monitoring of the location is realized, the treatment quality would be improved. We have developed an electron-tracking Compton camera (ETCC) for real-time monitoring on the proton therapy. Our ETCC has a wide energy dynamic range of 200-1300 keV and a wide field of view. Therefore, ETCC has a potential as a quality assurance tool for proton therapy. We simulated and conducted an experiment with a 155 MeV proton beam and a water phantom. We succeeded in imaging a Bragg peak with prompt gamma rays.

Waveform simulation based on 3D dose distribution for acoustic wave generated by proton beam irradiation

A pulsed proton beam is capable of generating an acoustic wave when it is absorbed by a medium. This phenomenon suggests that the acoustic waveform produced may well include information on the three-dimensional (3D) dose distribution of the proton beam. We simulated acoustic waveforms by using a transmission model based on the Green function and the 3D dose distribution. There was reasonable agreement between the calculated and measured results. The results obtained confirm that the acoustic waveform includes information on the dose distribution.

Displacement of hepatic tumor at time to exposure in end-expiratory-triggered-pulse proton therapy.

PURPOSEnThis study is to evaluate reproducibility of hepatic tumors in end-expiration and end-inspiration on free-breathing, also measure shift of hepatic tumor location in pulsed proton beams exposure in end-expiration in order to estimate feasible planning target volume (PTV) margin.nnnMATERIALS AND METHODSnPairs (1232) of anterior and lateral radiographs from 30 patients (628 end-expiration and 604 end-inspiration phases) were analyzed using fiducial markers adjacent to the tumors. By using the co-ordinates of the marker centroid of mass related to the isocenter, intrafractional variation was compared in end-expiration and end-inspiration, and a feasible PTV margin was generated using the measured motion.nnnRESULTSnThe average internal motion in end-expiration was 1.1mm, which was significantly smaller than that in end-inspiration. The mean deviation from the plan was -0.1, 0.3, and 0.1mm in the left-right (LR), cranio-cepharal (CC), and anterior-posterior (AP) directions, respectively. The estimated PTV margins were 3.2, 3.5, and 4.6mm, in the LR, CC, and AP directions, respectively.nnnCONCLUSIONSnIt was indicated that localization of the targets was more reproducibility in end-expiration than that in end-inspiration. Also, feasible and practical margin values were obtained. These should contribute accuracy of respiration synchronized proton radiotherapy for liver tumors.

Experimental Evaluation of Pencil Beam Algorithm by Measurements of Dose Distributions of Protons Traversing an L-Shaped Phantom

A proton dose-calculation method has been developed on the basis of the pencil-beam algorithm (PBA), which is expected to improve the precision of the conventional method based on the broad-beam algorithm (BBA). In order to verify the accuracy of calculation by the PBA, dose distributions formed by a horizontal proton beam traversing a phantom with an L-shaped horizontal cross section were measured using a silicon semiconductor detector (SSD) in a water vessel. The results of the measured dose distributions agree well with the ones calculated using the PBA within an rms error of 2.3%. Therefore, the dose-calculation method by the PBA is useful and applicable to actual treatment planning of the proton therapy.

RBE and OER within the spread-out Bragg peak for proton beam therapy: in vitro study at the Proton Medical Research Center at the University of Tsukuba.

There are few reports on the biological homogeneity within the spread-out Bragg peak (SOBP) of proton beams. Therefore, to evaluate the relative biological effectiveness (RBE) and the oxygen enhancement ratio (OER), human salivary gland tumor (HSG) cells were irradiated at the plateau position (position A) and three different positions within a 6-cm-wide SOBP (position B, 26 mm proximal to the middle; position C, middle; position D, 26 mm distal to the middle) using 155-MeV/n proton beams under both normoxic and hypoxic conditions at the Proton Medical Research Center, University of Tsukuba, Japan. The RBE to the plateau region (RBEplateau) and the OER value were calculated from the doses corresponding to 10% survival data. Under the normoxic condition, the RBEplateau was 1.00, 0.99 and 1.09 for positions B, C and D, respectively. Under the hypoxic condition, the RBEplateau was 1.10, 1.06 and 1.12 for positions B, C and D, respectively. The OER was 2.84, 2.60, 2.63 and 2.76 for positions A, B, C and D, respectively. There were no significant differences in either the RBEplateau or the OER between these three positions within the SOBP. In conclusion, biological homogeneity need not necessarily be taken into account for treatment planning for proton beam therapy at the University of Tsukuba.

Lineal energy-based evaluation of oxidative DNA damage induced by proton beams and X-rays

Abstract Purpose: To determine the oxidative capabilities of proton beams compared to X-rays based on lineal energy (y). Materials and methods: Microdosimetry was used to determine y-values of 155 MeV protons. Salmon testes deoxyribonucleic acid (ST-DNA) in solution and human tumor cells (MOLT-4) were irradiated with 200 kV X-rays (X) or 155 MeV protons at their plateau (P) and near their Bragg-peak (B). 8-Hydroxydeoxyguanosine (8-OHdG) production was determined by high performance liquid chromatography. Double-strand breaks (DSB) in ST-DNA were evaluated by agarose gel electrophoresis and DSB in cell nuclei were evaluated by immunocytochemical analysis of phosphorylated histone H2AX (γH2AX) foci. Edaravone was used as a radical scavenger. Results: 8-OHdG yields in ST-DNA were significantly higher with X than with P or B, and they were significantly higher with P than with B. DSB yields in ST-DNA were higher with P than with B or X, although not statistically significant, and were nearly equal with B and X. Although γH2AX foci formation in MOLT-4 cells after each irradiation type was nearly identical, the addition of edaravone significantly inhibited foci formation only with X. Conclusions: Our results indicated that radical-induced indirect DNA damage was significantly lower with proton beams than with X-rays.

Feasibility study on using imaging plates to estimate thermal neutron fluence in neutron-gamma mixed fields.

In current radiotherapy, neutrons are produced in a photonuclear reaction when incident photon energy is higher than the threshold. In the present study, a method of discriminating the neutron component was investigated using an imaging plate (IP) in the neutron-gamma-ray mixed field. Two types of IP were used: a conventional IP for beta- and gamma rays, and an IP doped with Gd for detecting neutrons. IPs were irradiated in the mixed field, and the photo-stimulated luminescence (PSL) intensity of the thermal neutron component was discriminated using an expression proposed herein. The PSL intensity of the thermal neutron component was proportional to thermal neutron fluence. When additional irradiation of photons was added to constant neutron irradiation, the PSL intensity of the thermal neutron component was not affected. The uncertainty of PSL intensities was approximately 11.4 %. This method provides a simple and effective means of discriminating the neutron component in a mixed field.

Measurement of the Polarization of \(\varLambda^{0}\) Hyperons Produced Inclusively by 12-GeV Protons on Tungsten

The polarization of 2.4×10 5 (varLambda^{0}) hyperons has been measured in inclusive production by 12- GeV protons on tungsten at three production angles, 3.5°, 6.5°, and 9.5°. In terms of Feynmans x F and the transverse momentum p T of (varLambda^{0}), the kinematic range is 0.3≦ x F ≦0.8 and 0.4≦ p T ≦1.6 GeV/c. The (varLambda^{0}) was identified by detecting the proton and pion from the (varLambda^{0}{rightarrow}ppi^{-}) decay with a double-stage magnetic spectrometer, and its polarization was determined from a hybrid Monte Carlo analysis on asymmetries in the angular distribution of the decay products. The observed polarization is consistent with the data obtained at higher energies, indicating that the phenomenon of the inclusive (varLambda^{0}) polarization scales down to the 12-GeV region. The polarization at 12 GeV increases linearly with p T up to 16% at p T =1.0 GeV/c, showing a tendency to level off above that point.

Convenient Method of Thermal Neutron Measurement Using Imaging Plates in Proton Therapy

In proton therapy, measurement of secondary neutron emission is important, because such radiation can influence the occurrence of secondary cancers and the radioactivity of the treatment room. In this study, we investigated the possibility of neutron detection using a neutron imaging plate (IP) and a general IP.