Combined proton-neutron therapy can be the best opportunity for neutron radiation therapy due to highly conformal proton irradiation and high relative biological effectiveness of neutrons. The study compares 4 schemes of sequential in vitro exposure of Chinese hamster fibrosarcoma cells B14-150 to 14.5 MeV neutrons and a scanning beam of protons. Treatment efficiency increased with increasing the contribution of the neutron component to the total dose from 30 to 40% and the delivery of the neutron dose as the first fraction in the two-fraction proton-neutron exposure.

Proton and ion radiation therapy, when used both as single radiation and in mixed radiation mode, have a number of advantages over the conventional γ-therapy that are determined by physical characteristics of accelerated particles. The paper presents the results of an in vitro study of the effectiveness of sequential exposures of Chinese hamster tumor cells B14-150 to proton (p) and 12 C ion beams. We used 4 irradiation schemes differing by the sequence of exposure and the contribution of each radiation to the total dose. Synergism was shown for 12 C ions dose contribution of 45% (taking into account the coefficient of relative biological efficiency) and the sequence 12 C→p.

We studied the effects of single and combined action of protons and carbon ions 12 C 6+ on the pool of MCF-7 human breast cancer stem cells. Single irradiation with a beam of protons or carbon ions had no significant effects on the relative number of cancer stem cells (CSC). The effects of combined irradiation in a total equieffective dose of 4 Gy depended on the sequence of exposure to ionizing radiations: the relative number of CSC did not change after irradiation with carbon ions and then with protons, but increased in the case of the reverse sequence. The most favorable result, i.e . a decrease in the CSC pool, was observed in the case of sequential irradiation with carbon ions and protons and their equal contribution to total equieffective dose. In this case, the absolute number of CSC decreased by on average 2.1 times in comparison with the control ( p <0.05). The revealed regularities are of interest for the further development of new methods of radiation therapy.

The use of radiation with low and high linear energy transfer (LET) in the same treatment regimen is promising in terms of increasing the efficiency and reducing the severity of radiation complications. Here we studied combined effect of protons (LET≈3 keV/μm) and heavy recoils (HR) induced by 14.5 MeV neutrons (LET≈290 keV/μm) on B14-150 fibrosarcoma cells. Comparison of the 4 irradiation schemes with different high-LET/low-LET dose ratios and the irradiation sequences revealed higher effectiveness of the combined action in the HR→protons sequence and with increasing HR dose contribution to 40% of the total dose. The observed effects were due to differences in the recovery of damages induced in cells by radiations with low and high LET.

The development of technologies for using the Novac-11 pulsed electron accelerator in radiation therapy of animals with spontaneous neoplasms requires dosimetric and radiobiological studies. The studies were performed on cultured Chinese hamster V-79 fibroblasts after irradiation with 10 MeV electrons in a dose range up to 12 Gy and 60Co γ-radiation. Chemical dosimeters FBX and Fricke were used as additional test-systems. The depth dose curves were measured and the maximum dose depth of the electron beam was determined in tissue-equivalent phantoms. Cell survival and the data of chemical dosimetric systems showed that the effects of electron irradiation did not differ from that of 60Co γ-radiation. It was concluded that the use of Novac-11 in the therapy of animals with spontaneous neoplasms is advisable.

The paper investigates the characteristics of the chemical Fricke dosimeter (with the standard composition (D1), without NaCl addition to the solution (D2), without NaCl but with a tenfold increased concentration of Fe2+ (D3)) under continuous and pulsed irradiation with an ultra-high dose rate of the BARS-6 reactor with unshielded metallic cores. The dosimeter radiosensitivity had a linear dependence on the gamma neutron radiation dose in a range of 25 to 750 Gy and was respectively 1.96 ± 0.05 μGy–1 (D1), 2.04 ± 0.05 μGy–1 (D2), and 2.08 ± 0.5 μGy–1 (D3) in the continuous irradiation mode, and 1.24 ± 0.05 μGy–1, 2.00 ± 0.05 μGy–1, and 1.94 ± 0.05 μGy–1 in the pulsed irradiation mode. This makes ≈ 60% of their sensitivity to the 60Со gamma radiation (3.40 ± 0.02 μGy–1), and 36%, 1.6 times as less, for a standard Fricke dosimeter irradiated in the pulsed mode. The experimental value of the radiation chemical yield, Gn(Fe3+), for all solution modifications and both irradiation modes varied slightly and was 0.84 ± 0.11 μM/J on the average, except for the standard solution in the pulsed mode (0.66 ± 0.07 μM/J). The neutron doses determined by chemical and activation dosimeters coincided within the error limits, but the chemical dosimeter readings were systematically higher, by about 20%. Therefore, in the fission spectrum neutron dose rate range of 0.4 to 7×108 Gy/min, there is no dose rate effect both in the standard Fricke dosimeter version (without NaCl) and in the modified version, which makes it possible to use modified Fricke dosimeters to assess the physical and dosimetry characteristics of mixed gamma neutron radiation beams.

The study presents results of investigations on chromosome aberrations (CA) yield in Chinese ham-ster ovary cells after exposure to gamma-rays and accelerated carbon ions (455 MeV/amu) at doses less than 1 Gy in the pristine Bragg curve plateau and behind the Bragg peak, where normal tissues are situated in the course of radiotherapy. Initial parts of dose curves for total CA and terminal deletions frequencies differed from linear-quadratic dependence and the region of induced radioresistance were observed at 0.1-0.6 Gy for gamma-rays. The similar curve shapes were detected for carbon ions, but plateau region was shorter (0.15-0.35 Gy). Despite the uniform shape of the dose curves for the CA yield, a definite dependence of the cytogenetic effect on the linear energy transfer (LET) is observed. The CA frequency increased with LET rising in the order: gamma-irradiation (0.2 keV/μm), carbon ions at the Bragg curve plateau (10-12 keV/μm) and at the «tail» of Bragg peak (25-27 keV/μm). Outside this range, the yield of chromosome aberrations also enhanced with increasing LET in the same order. The results obtained confirm that the hypersensitivity and induced radioresistance phenomena are characteristic for low level exposure to low-LET and middle-LET radiations when chromosome aberration test is used.

Obninsk In highly conformal proton therapy treatments it is very important that doses calculated with the use of the treatment planning system (TPS) and virtual absorbed doses to a tumor and surrounding tis-sues should coincide. This requirement is necessary to be fulfilled, in order to protect surrounding healthy organs and tissues. The purpose of the study is to estimate possibility of using chemical dosimetry for measuring an absorbed dose and verification of the computed TPS doses when dose is delivered to a target volume at one or several different angles. The high sensitivity FBX-system (Ferrous (II) sulfate – Benzoic acid v Xylenol orange) served as a dosimeter. We performed irradia-tions at the proton accelerator “Prometheus” (manufacturer – PROTOM, Protvino, Russia) from one and three directions (0°, 90°, 180°) in three different ways: from one direction either with one dose fraction or with several fractions of 1 Gy; and from three directions with one dose fraction, the pre-scribed total dose being equal for all scenarios. The dose range was 1-5 Gy. The results obtained with the FBX-dosimeter show that there are no statistically significant differences between the dose delivery methods (one or three fields, one or several dose fractions). Comparison of the proton irradiation data with the calibration curve for 60 Co  -radiation shows significant differences, which we explain by different values of linear energy transfer for protons (LET range ~5–20 keV/μm) and 60 Со  -radiation (~0.25-0.3 keV/μm). The data obtained allow to conclude that in the clinical and experimental dosimetry of scanning proton beams, the FBX dosimetric system can be used effec-tively. It also points out the necessity to consider the dose average LET in the TPS to enhance the therapy efficiency and quality assurance. However, one must preliminary calibrate the FBX dosimeter under the same proton energy-LET conditions as in the tested TPS dose distributions for suc-cessful use in clinical

The results of the protons biological effectiveness on tumor cells under hypofractionated irradiation with the division of a single (daily) dose into two, three, and four equal fractions (ultrafractionation) are presented. The proposed schemes for splitting the daily dose into fractions were selected in order to reduce the dose to healthy tissues and critical organs located at the proton beam pathway.

Dose-dependences of the chromosomal aberrations induction in B14-150 cells were studied for carbon ions (E ∼455 MeV/nucleon) with different values of the linear energy transfer (LET): 10-12 keV/μm (proximal region of the Bragg curve - plateau) and 25-27 keV/μm (tail of the Bragg curve). It is shown that the level of chromosome aberrations was higher for irradiation at tail of carbon beam. The dose relations were described by a modified linear-quadratic model and had a similar character in the studied dose range of 0.05-2.5 Gy. A sharp increase of the chromosome aberrations yield at the dose range up to 0.1 Gy (hyper-radiosensitivity, HRS), slowdown in it at the range of 0.1-0.3 Gy (induced radioresistance, IRR) and a further its’ growth above 0.3 Gy were observed with a transformation to linear and linear-quadratic dependences. The results obtained agree with the known literature data and indicates the likeness of the biological effect of hyper-radiosensitivity and induced radioresistance (HRS/IRR) for different cell lines.

Сравнение биологической эффективности ускоренных ионов углерода и тяжёлых ядер отдачи на клетках китайского хомячкаКорякина Е.В. 1 , Потетня В.И. 1 , Трошина М.В. 1 , Ефимова М

A method for determining doses absorbed by biological objects on irradiation with neutrons from portable generators with energies of about 14.1 MeV was developed. The contributions of each of the components of the radiation field to the total dose were analyzed and introduced errors were assessed, permitting irradiation schemes to be optimized. Determination of dose from the intensity of neutron release from the target, despite a rather large introduced error, is quicker and more convenient than direct measurement with a dosimeter.

Abstract: There is a necessary requirement to provide precise dosimetry measurements for radiotherapy and radiobiological studies in the proton beams. The most common practice nowadays to obtain the dose distribution is the use of ionization chambers. However, for many needs, it is also required to estimate an average absorbed dose in the target, while the targets themselves might have complex geometries and large volumes. One of the recent successful method for such measurement is the chemical dosimetry using FBX solutions coupled with the additive manufacturing, which can ensure the accurate representation of complex target geometries. In this study, we chose an optimal chemically neutral material for 3D printing that is not reacting with any of FBX compounds, manufactured the sealed waterproof target models with complex geometry and performed preliminary measurements of the average absorbed dose in a number of volumes representing the different shapes of the targets. The obtained results strongly confirm the possibility of the use of the presented technology for practical dosimetry of proton beams.

We describe a technique for attaining extended transversally-flat paraxial dose fields with the intermediateenergy carbon beam slowly extracted at the magnetic-field flat-bottom from the IHEP U-70 synchrotron. To this end, a fixed-radius circular beam sweep with the aid of a compact electromechanical wobbler with rotating permanent dipole magnets is applied. A technique for tuning the beam transfer line and the irradiation facility proper at the interim radiobiological workbench with an external fixed target is substantiated. A brief description of its engineering implementation is presented. Results of the successful experimental verification of the technique in question with a carbon nuclear beam from the U-70 machine are reported, in particular, results of the primary radiobiological exercises accomplished in cooperation with the scientists at the MRRC of the Russian Ministry of Healthcare.