Feasibility of medical radioisotope production based on the proton beams at China Spallation Neutron Source

The utilization of a proton beam from the China Spallation Neutron Source(CSNS)for producing medical radioisotopes is appealing owing to its high current intensity and high energy.The medical isotope production based on the proton beam at the CSNS is significant for the development of future radiopharmaceuticals,particularly for theα-emitting radiopharmaceu-ticals.The production yield and activity of typical medical isotopes were estimated using the FLUKA simulation.The results indicate that the 300-MeV proton beam with a power of 100 kW at CSNS-II is highly suitable for proof-of-principle studies of most medical radioisotopes.In particular,this proton beam offers tremendous advantages for the large-scale production of alpha radioisotopes,such as 225Ac,whose theoretical production yield can reach approximately 57 Ci/week.Based on these results,we provide perspectives on the use of CSNS proton beams to produce radioisotopes for medical applications.

Collection efficiency of a monitor parallel plate ionization chamber for pencil beam scanning proton therapy

The collection efficiency of monitor parallel plate ionization chambers is the main uncertainty in the beam control of pencil beam scanning systems.Existing calculation methods for collection efficiency in photon or passive scattering proton systems have not considered the characteristics of non-uniform charge density in pencil beam scanning systems.In this study,Boag’s theory was applied to a proton pencil beam scanning system.The transverse distribution of charge density in the ionization chamber was considered to be a Gaussian function and an analytical solution was derived to calculate collection efficiency in the beam spot area.This calculation method is called the integral method and it was used to investigate the effects of beam parameters on collection efficiency.It was determined that collection efficiency is positively correlated with applied voltage,beam size,and beam energy,but negatively correlated with beam current intensity.Additionally,it was confirmed that collection efficiency is improved when the air filling the monitor parallel plate ionization chamber is replaced with nitrogen.

Impact of Low-Energy Ion Beam Implantation on the Expression of Ty1-copia-like Retrotransposons in Wheat(Triticum aestivum)

Retrotransposon-like elements are major constituents of most eukaryotic genomes. For example, they account for roughly 90% of the wheat （Triticum aestivum） genome, Previous study on a wheat strain treated by low-energy N^＋ ions indicated the variations in AFLP （Amplified Fragment Length Polymorphism ） markers, One such variation was caused by the re-activation of Tyl-copia-like retrotransposons, implying that the mutagenic effects of lowenergy ions might work through elevated activation of retrotransposons, In this paper an expression profile of Tyl-copia-like retrotransposons in wheat treated by low-energy N^＋ ions is reported, The reverse transcriptase （RT） domains of these retrotransposons were amplified by reverse-transcriptional polymerase chain reaction （RT-PCR） and sequentially cloned, 42 and 65 clones were obtained from the treated （CL） and control materials （CK）, respectively, Sequence analysis of each clone was performed by software. Phylogeny and classification were calculated responding to the sequences of the RT domains. All the results show that there is much difference in the RT domain between the control sample and the treated sample, Especially, the RT domains from the treated group encode significantly more functional ORF （open reading frames） than those from the control sample, This observation suggests that the treated sample has higher activation of retrotransposons, possibly as a consequence of low-energy ion beam irradiation, It also suggests that retrotransposons in the two groups impact the host gene expression in two different ways and carry out different functions in wheat cells.

A segmented conical electric lens for optimization of the beam spot of the low-energy muon facility at PSI: a Geant4 simulation analysis

The low-energy muon facility at PSI provides nearly fully polarized positive muons with tunable energies in the ke V range to carry out muon spin rotation(LE-μSR)experiments with nanometer depth resolution on thin films,heterostructures, and near-surface regions. The low-energy muon beam is focused and transported to the sample by electrostatic lenses. In order to achieve a minimum beam spot size at the sample position and to enable the steering of the beam in the horizontal and vertical direction, a special electrostatic device has been implemented close to the sample position. It consists of a cylinder at ground potential followed by four conically shaped electrodes,which can be operated at different electric potential. In LE-μSR experiments, an electric field at the sample along the beam direction can be applied to accelerate/decelerate muons to different energies(0.5–30 keV). Additionally, a horizontal or vertical magnetic field can be superimposed for transverse or longitudinal field μSR experiments. The focusing properties of the conical lens in the presence of these additional electric and magnetic fields have been investigated and optimized by Geant4 simulations. Some experimental tests were also performed and show that the simulation well describes the experimental setup.

Radiation-hardened property of single-walled carbon nanotube film-based field-effect transistors under low-energy proton irradiation

Strong C-C bonds,nanoscale cross-section and low atomic number make single-walled carbon nanotubes(SWCNTs)a potential candidate material for integrated circuits(ICs)applied in outer space.However,very little work combines the simulation calculations with the electrical measurements of SWCNT field-effect transistors(FETs),which limits further understanding on the mechanisms of radiation effects.Here,SWCNT film-based FETs were fabricated to explore the total ionizing dose(TID)and displacement damage effect on the electrical performance under low-energy proton irradiation with different fluences up to 1×1015 p/cm2.Large negative shift of the threshold voltage and obvious decrease of the on-state current verified the TID effect caused in the oxide layer.The stability of the subthreshold swing and the off-state current reveals that the displacement damage caused in the CNT layer is not serious,which proves that the CNT film is radiation-hardened.Specially,according to the simulation,we found the displacement damage caused by protons is different in the source/drain contact area and channel area,leading to varying degrees of change for the contact resistance and sheet resistance.Having analyzed the simulation results and electrical measurements,we explained the low-energy proton irradiation mechanism of the CNT FETs,which is essential for the construction of radiation-hardened CNT film-based ICs for aircrafts.

Continuous operation of 2.45-GHz microwave proton source for 306 hours with more than 50 mA DC beam

This paper describes a long-term operation of the 2.45-GHz microwave proton source at Peking University. The DC proton beam of 50–55 mA with energy of 35 keV has been run for 306 hours continuously. Total beam availability,defined as 35-keV beam-on time divided by elapsed time, is higher than 99%. Water cooling machine failures cause all the downtime, and no plasma generator failure or high voltage breakdown is observed. The longest uninterrupted run time is122 hours.

Design and development of the beamline for a proton therapy system

A proton therapy(PT)facility with multiple treatment rooms based on the superconducting cyclotron scheme is under development at Huazhong University of Science and Technology(HUST).This paper attempts to describe the design considerations and implementation of the PT beamline from a systematic viewpoint.Design considerations covering beam optics and the influence of high-order aberrations,beam energy/intensity modulation,and beam orbit correction are described.In addition to the technical implementation of the main beamline components and subsystems,including the energy degrader,fast kicker,beamline magnets,beam diagnostic system,and beamline control system are introduced.

Design of 50 MeV proton microbeam based on cyclotron accelerator

High-energy proton microbeam facilities are powerful tools in space science,biology and cancer therapy studies.The primary limitations of the 50 MeV proton microbeam system are the poor beam quality provided by the cyclotron and the problem of intense scattering in the slit position.Here,we present an optical design for a cyclotron-based 50 MeV high-energy proton microbeam system with a micron-sized resolution.The microbeam system,which has an Oxford triplet lens configuration,has relatively small spherical aberrations and is insensitive to changes in the beam divergence angle and momentum spread.In addition,the energy filtration included in the system can reduce the beam momentum spread from 1 to 0.02%.The effects of lens parasitic aberrations and the lens fringe field on the beam spot resolution are also discussed.In addition,owing to the severe scattering of 50 MeV protons in slit materials,a slit system model based on the Geant4 toolkit enables the quantitative analysis of scattered protons and secondary particles.For the slit system settings under a 10-micron final beam spot,very few scattered protons can enter the quadrupole lens system and affect the focusing performance of the microbeam system,but the secondary radiation of neutrons and gamma rays generated at the collimation system should be considered for the 50 MeV proton microbeam.These data demonstrate that a 50 MeV proton microbeam system with a micron-sized beam spot based on a cyclotron is feasible.

Reformatted method for two-dimensional detector arrays measurement data in proton pencil beam scanning

The spatial resolution of a commercial two-dimensional(2D)ionization chamber(IC)array is limited by the size of the individual detector and the center-to-center distance between sensors.For dose distributions with areas of steep dose gradients,inter-detector dose values are derived by the interpolation of nearby detector readings in the conventional mathematical interpolation of 2D IC array measurements.This may introduce significant errors,particularly in proton spot scanning radiotherapy.In this study,by combining logfile-based reconstructed dose values and detector measurements with the Laplacian pyramid image blending method,a novel method is proposed to obtain a reformatted dose distribution that provides an improved estimation of the delivered dose distribution with high spatial resolution.Meanwhile,the similarity between the measured original data and the downsampled logfilebased reconstructed dose is regarded as the confidence of the reformatted dose distribution.Furthermore,we quantify the performance benefits of this new approach by directly comparing the reformatted dose distributions with 2D IC array detector mathematically interpolated measurements and original low-resolution measurements.The result shows that this new method is better than the mathematical interpolation and achieves gamma pass rates similar to those of the original low-resolution measurements.The reformatted dose distributions generally yield a confidence exceeding 95%.

Beam charge integration in external beam PIXE–PIGE analysis utilizing proton backscattering with an extraction window

In this study,we present a new method for the indirect integration of beam charges in external beam proton-induced X-ray emission and proton-induced c-ray emission(PIXE–PIGE) analysis.We recorded proton spectra backscattered by a Kapton film extraction window in different sample situations and under different beam currents.We also simulated backscattering spectra using the simulation of backscattering spectra program(SIMNRA).We determined that in a specific geometrical arrangement,different sample situations did not significantly affect factor C_Q(the ratio between integral backscattering proton counts and integral beam charges).We also studied the reproducibility and beam current dependence of factor C_Q.The statistic factor of C_Q was28.95 ± 0.6 kilo counts/l C,with a relative standard deviation of 2.0 %.Significantly,in external beam PIXE–PIGE analysis,we were able to calculate beam charge integration from the integral backscattering proton counts in an energy region.

New progress on beam availability and reliability of PKU high intensity CW proton ECR ion source

The stability and reliability of an ion source and its beam availability are extremely significant for any accelerator,especially for those high current long term CW operation ones like ADS. Although the first high quality 306-hours continuous wave（CW） operating curve at 50 m A@35 ke V has been successfully obtained with a standard compact 2.45 GHz ECR ion source at Peking University（PKU）, but the uncertainties that caused beam trips before are unacceptable during an accelerator real operation and should be eliminated. Meanwhile, no permission will be given when the beam power is upgraded from 50 m A@35 ke V to 50 m A@50 ke V. To improve the PKU CW proton source quality, several upgrades were done recently. After those improvements, a new long term CW proton beam experiment at 50 m A@50 ke V was carried out in June 2016. The total running time is 300.5 hours, including near 6 hours ion source preparation and 294 hours non-disturb continuous operation. Within the continuous 13 days operation, no beam-off happened, no spark was observed,no beam drop appeared, no interrupting action was needed, and only a few beam fluctuations caused by the air conditional failure occurred. Beam availability and reliability within the 294 hours is 100%. The root-mean-square（RMS） emittance of this 50 m A@50 ke V CW proton beam is about 0.186 π.mm.mrad. A careful inspection of the ion source was done after this long term operation and no obvious damage was found. The restart experimental results obtained after the ion source inspection prove the high repeatability of PKU PMECRIS. In addition, a 130-m A H＋beam was obtained at 50 k V with duty factor of 10%（100 Hz/1 ms） with this source. Details will be presented in this paper.

Supercontinuum Generation in Lithium Niobate Ridge Waveguides Fabricated by Proton Exchange and Ion Beam Enhanced Etching

We report on the fabrication of the lO-mm-long lithium niobate ridge waveguide and its supercontinuum gen- eration at near-visible wavelengths （around 800hm）. The waveguides are fabricated by a combination of MeV copper ion implantation followed by wet etching in a proton exchanged lithium niobate planar waveguide. Using a mode-locked Ti：sapphire laser with a central wavelength of 800nm, the generated broadest supereontinuum through the ridge waveguides spans 302 nm （at -30 dB points）, from 693 to 995 nm. Temporal coherence proper- ties of the supercontinuum are experimentally studied by a Michelson interferometer and the coherence length of the broadest supercontinuum is measured to be 5.2 μm. Our results offer potential for a compact and integrated supercontinuum source for applications including bio-imaging, spectroscopy and optical communication.

Generating Proton Beams Exceeding 10 MeV Using High Contrast 60TW Laser

A prototype of a laser driven proton accelerator is built at Peking University. Protons exceeding IOMeV are accelerated from micrometer-thick aluminum targets irradiated by tightly focused laser pulse with 1.8 J energy and 30fs duration. The beam energy spectrum and charge distribution are measured by a Thomson parabola spectrometer and radiochromic fihn stacks. The sensitivity of proton cut-off energy to the focusing of the laser beam, the pulse duration, and the foil thickness are systematically investigated in the experiments. Stable proton beams have been produced with an optimized parameter set, providing a cornerstone for the future applications of laser accelerated protons.

Beam optics study for energy selection system of SC200 superconducting proton cyclotron

To meet the demands on proton therapy in Russia and China, JINR and ASIPP have started to develop a proton therapy facility based on an isochronous superconducting proton accelerator. A 200 Me V/500 n A proton beam will be extracted from the SC200 superconducting proton cyclotron. Due to the energy of the cyclotron being fixed, an energy selection system(ESS) is employed to degrade such energy in order to match the particle energy to a shallower depth. In this article, calculation of beam optics, analysis of beam transmission, and correction of orbit distortion are presented. Studies show that the main factors influencing transmission efficiency of the SC200 ESS beamline are the degrader, collimator, slit, vacuum system, beam diagnostic system, and trajectory correction system. Through the beam optics study, the designed ESS beamline can provide 70–200 Me V proton beam to a treatment room, with a maximum emittance of24 p mm mrad. Also, the controllable momentum spread ranges from 0.1 to 1.0%, which is equivalent to an energy spread from 0.193 to 1.93%. The transmission efficiency about 0.204% can be obtained when the emittance is24 p mm mrad with an energy spread of ± 0.6%.

Numerical Approach of Interactions of Proton Beams and Dense Plasmas with Quantum-Hydrodynamic/Particle-in-Cell Model

A one dimensional quantum-hydrodynamic/particle-in-cell （QHD/PIC） model is used to study the interaction process of an intense proton beam （injection density of 1017 cm-3） with a dense plasma （initial density of -10^21 cm^-3）, with the PIC method for simulating the beam particle dynamics and the QHD model for considering the quantum effects including the quantum statistical and quantum diffraction effects. By means of the QHD theory, the wake electron density and wakefields are calculated, while the proton beam density is calculated by the PIC method and compared to hydrodynamic results to justify that the PIC method is a more suitable way to simulate the beam particle dynamics. The calculation results show that the incident continuous proton beam when propagating in the plasma generates electron perturbations as well as wakefields oscillations with negative valleys and positive peaks where the proton beams are repelled by the positive wakefields and accelerated by the negative wakefields. Moreover, the quantum correction obviously hinders the electron perturbations as well as the wakefields. Therefore, it is necessary to consider the quantum effects in the interaction of a proton beam with cold dense plasmas, such as in the metal films.

Proton beam therapy for locally advanced lung cancer: A review

Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy(PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon(X-ray) radiotherapy(XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk(lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity comparedto XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer.

Proton beam therapy in apneic oxygenation treatment of an unresectable hepatocellular carcinoma: A case report and review of literature

Presented here is the clinical course of a 63-yearold patient with a central, large and unresectable hepatocellular carcinoma(HCC) with liver metastases and tumor invasion of the portal and hepatic veins. After the tumor had been diagnosed, the patient was immediately treated with proton beam therapy(PBT), at a total dose of 60 Gy(relative biological effectiveness) in 20 fractions administered within 4 wk. To manage the respiratory movements, at the Rinecker Proton Therapy Center, apneic oxygenation was given daily, under general anesthesia. The patient tolerated both the PBT and general anesthesia very well, and did now show any signs of acute or late toxicity. The treatment was followed by constant reductions in the tumor marker alpha-fetoprotein and the cholestatic parameters gamma-glutamyltransferase and alkaline phosphatase. The patient commenced an adjuvant treatment with sorafenib, given at 6-wk intervals, after the PBT. Follow-up with regular magnetic resonance imaging has continued for 40 mo so far, demonstrating remarkable shrinkage of the HCC(maximal diameter dropping from approximately 13 cm to 2 cm). To date, the patient remains free of tumor recurrence. PBT served as a safe and effective treatment method for an unresectable HCC with vascular invasion.

Reirradiation of recurrent breast cancer with proton beam therapy:A case report and literature review

BACKGROUND Locoregional recurrence of breast cancer is challenging for clinicians,due to the various former treatments patients have undergone.However,treatment of the recurrence with systemic therapy and subsequent reirradiation of chest wall is accompanied by increased toxicities,particularly radiation-induced cardiovascular disease.Reirradiation by proton beam therapy(PBT)enables superior preservation of adjacent organs at risk as well as concurrent dose escalation for delivery to the gross tumor.This technology is expected to improve the overall outcome of recurrent breast cancer.CASE SUMMARY A 47-year-old female presented with an extensive locoregional recurrence at 10 yr after primary treatment of a luminal A breast cancer.Because of tumor progression despite having undergone bilateral ovarectomy and systemic therapy,the patient was treated with PBT BE total dose of 64.40 Gy to each gross tumor and 56.00 Gy to the upper mediastinal and retrosternal lymphatics including the entire sternum in 28 fractions.Follow-up computed tomography showed a partial remission,without evidence of newly emerging metastasis.At 19 mo after the PBT,the patient developed a radiation-induced pericardial disease and pleural effusions with clinical burden of dyspnea,which were successfully treated by drainage and corticosteroid.Cytological analysis of the puncture fluid showed no malignancy,and the subsequent computed tomography scan indicated stable disease as well as significantly decreased pericardial and pleural effusions.The patient remains free of progression to date.CONCLUSION PBT was a safe and effective method of reirradiation for locoregionally recurrent breast cancer in our patient.

Periodic Measurements of Passive Proton Beam Width Using Radiochromic Film in Fixed Gantry System

Background and Aim: Irradiation methods such as double scattering method and spot scanning method have been used in proton beam treatment devices. In the scattering method, a ridge filter or a range modulation wheel is used to create a spread-out Bragg peak, but the distribution at the patient position may change due to positional deviation of the incident beam. Therefore, assessment of the incident position of the beam is very important even in the scattering method. To investigate the width and distribution of the proton beam before entering the RMW, a radiochromic film was installed at the outlet of the transport pipe and the entrance of the profile-monitoring detector. Methods: In this study, the distributions of the beam at the exit of the transport pipe and the entrance of the monitor detector were measured using films. The beam width was measured from the full width at half maximum of the profile obtained from the distribution. Measurements were conducted every month for 10 months. Results: Beams of widths ranging from 1.82 to 2.30 mm in the horizontal direction and 4.25 to 5.33 mm in the vertical direction were outputted from the exit of the transport pipe. Beams of widths ranging from 2.16 to 2.67 mm in the horizontal direction and 4.06 to 5.31 mm in the vertical direction were outputted from the entrance of the monitor detector. The maximum width fluctuation for 10 months was 0.55 mm in the horizontal direction and 1.26 mm in the vertical direction at the entrance of the monitor detector. Conclusions: The distribution was obtained before the proton beam was scattered by the scatterer, and then we propose a method to periodically measure and monitor the changes in the beam distributions every month.

Preliminary Result of Hyperfractionated High-Dose Proton Beam Radiotherapy for Pediatric Skull Base Chordomas

Objective: Proton beam therapy (PBT) may provide good local control for skull base chordoma and reduced toxicities, especially for pediatric patients. Methods: We evaluated the efficacy and safety of hyperfractionated high-dose PBT in6 pediatric patients with newly-diagnosed skull basechordoma who were treated with PBT at our institute from 2011 to 2015. The patients were 5 males and one female, and the median age was 9 years old (range: 5 - 13). All patients received surgery before PBT. The median period between surgery and PBT was 57 days (range: 34 - 129 days). The treatment dose was 78.4 GyE in 56 fractions (twice per day). Results: All patients received PBT without severe acute toxicity. The median follow-up period was 27 months (range: 21 - 71 months). At the last follow-up, all patients were alive and all tumors were well controlled. Acute and late toxicities were generally acceptable, with only grade 1 and 2 events. Late toxicities included growth hormone abnormality and cortical hormone abnormality. One patient needed growth hormone and cortical hormone replacement therapy. Conclusion: Although the number of pediatric patients was small, our overall findings in the 6 cases indicate that hyperfractionated high-dose PBT is safe and effective for pediatric patients with skull base chordoma.