Crater formation and deuterium production in laser irradiation of polymers with implanted nano-antennas.

Recent validation experiments on laser irradiation of polymer foils with and without implanted golden nanoparticles are discussed. First we analyze characteristics of craters, formed in the target after its interaction with the laser beam. Preliminary experimental results show significant production of deuterons when both the energy of laser pulse and concentration of nanoparticles are high enough. We consider the deuteron production via the nuclear transmutation reactions p+C→d+X where protons are accelerated by the Coulomb field generated in the target plasma. We argue that maximal proton energy can be above threshold values for these reactions and the deuteron yield may noticeably increase due to presence of nanoparticles.

Lateral variations of radiobiological properties of therapeutic fields of 1H, 4He, 12C and 16O ions studied with Geant4 and microdosimetric kinetic model.

As known, in cancer therapy with ion beams the relative biological effectiveness (RBE) of ions changes in the course of their propagation in tissues. Such changes are caused not only by increasing the linear energy transfer (LET) of beam particles with the penetration depth towards the Bragg peak, but also by nuclear reactions induced by beam nuclei leading to the production of various secondary particles. Although the changes of RBE along the beam axis have been studied quite well, much less attention has been paid to the evolution of RBE in the transverse direction, perpendicular to the beam axis. In order to fill this gap, we simulated radiation fields of 1H, 4He, 12C and 16O nuclei of 20 mm in diameter by means of a Geant4-based Monte Carlo model for heavy-ion therapy connected with the modified microdosimetric kinetic model to describe the response of normal ([Formula: see text] Gy) and early-responding ([Formula: see text] Gy) tissues. Depth and radial distributions of saturation-corrected dose-mean lineal energy, RBE and RBE-weighted dose are investigated for passive beam shaping and active beam scanning. The field of 4He has a small lateral spread as compared with 1H field, and it is characterised by a modest lateral variation of RBE suggesting the use of fixed RBE values across the field transverse cross section at each depth. Reduced uncertainties of RBE on the boundary of a 4He treatment field can be advantageous in a specific case of an organ at risk located in lateral proximity to the target volume. It is found that the lateral distributions of RBE calculated for 12C and 16O fields demonstrate fast variations in the radial direction due to changes of dose and composition of secondary fragments in the field penumbra. Nevertheless, the radiation fields of all four projectiles at radii larger than 20 mm can be characterized by a common RBE value defined by tissue radiosensitivity. These findings can help, in particular, in accessing the transverse homogeneity of radiation fields of ions used in studies in vitro.

Distributions of deposited energy and ionization clusters around ion tracks studied with Geant4 toolkit.

The Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT) was extended to study the patterns of energy deposition at sub-micrometer distance from individual ion tracks. Dose distributions for low-energy (1)H, (4)He, (12)C and (16)O ions measured in several experiments are well described by the model in a broad range of radial distances, from 0.5 to 3000 nm. Despite the fact that such distributions are characterized by long tails, a dominant fraction of deposited energy (∼80%) is confined within a radius of about 10 nm. The probability distributions of clustered ionization events in nanoscale volumes of water traversed by (1)H, (2)H, (4)He, (6)Li, (7)Li, and (12)C ions are also calculated. A good agreement of calculated ionization cluster-size distributions with the corresponding experimental data suggests that the extended MCHIT can be used to characterize stochastic processes of energy deposition to sensitive cellular structures.

Comparative study of dose distributions and cell survival fractions for 1H, 4He, 12C and 16O beams using Geant4 and Microdosimetric Kinetic model.

Depth and radial dose profiles for therapeutic (1)H, (4)He, (12)C and (16)O beams are calculated using the Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT). (4)He and (16)O ions are presented as alternative options to (1)H and (12)C broadly used for ion-beam cancer therapy. Biological dose profiles and survival fractions of cells are estimated using the modified Microdosimetric Kinetic model. Depth distributions of cell survival of healthy tissues, assuming 10% and 50% survival of tumor cells, are calculated for 6 cm SOBPs at two tumor depths and for different tissues radiosensitivities. It is found that the optimal ion choice depends on (i) depth of the tumor, (ii) dose levels and (iii) the contrast of radiosensitivities of tumor and surrounding healthy tissues. Our results indicate that (12)C and (16)O ions are more appropriate to spare healthy tissues in the case of a more radioresistant tumor at moderate depths. On the other hand, a sensitive tumor surrounded by more resistant tissues can be better treated with (1)H and (4)He ions. In general, (4)He beam is found to be a good candidate for therapy. It better spares healthy tissues in all considered cases compared to (1)H. Besides, the dose conformation is improved for deep-seated tumors compared to (1)H, and the damage to surrounding healthy tissues is reduced compared to heavier ions due to the lower impact of nuclear fragmentation. No definite advantages of (16)O with respect to (12)C ions are found in this study.

Nanolesions induced by heavy ions in human tissues: Experimental and theoretical studies.

The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as "streaks" which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these "streaks" also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively.

Physics of ion beam cancer therapy: a multiscale approach.

We propose a multiscale approach to understand the physics related to ion-beam cancer therapy. It allows the calculation of the probability of DNA damage as a result of irradiation of tissues with energetic ions, up to 430 MeV/u. This approach covers different scales, starting from the large scale, defined by the ion stopping, followed by a smaller scale, defined by secondary electrons and radicals, and ending with the shortest scale, defined by interactions of secondaries with the DNA. We present calculations of the probabilities of single and double strand breaks of DNA, suggest a way to further expand such calculations, and also make some estimates for glial cells exposed to radiation.

PET monitoring of cancer therapy with 3He and 12C beams: a study with the GEANT4 toolkit.

We study the spatial distributions of beta(+)-activity produced by therapeutic beams of (3)He and (12)C ions in various tissue-like materials. The calculations were performed within a Monte Carlo model for heavy-ion therapy (MCHIT) based on the GEANT4 toolkit. The contributions from positron-emitting nuclei with T(1/2) > 10 s, namely (10,11)C, (13)N, (14,15)O, (17,18)F and (30)P, were calculated and compared with experimental data obtained during and after irradiation, where available. Positron-emitting nuclei are created by a (12)C beam in fragmentation reactions of projectile and target nuclei. This leads to a beta(+)-activity profile characterized by a noticeable peak located close to the Bragg peak in the corresponding depth-dose distribution. This can be used for dose monitoring in carbon-ion therapy of cancer. In contrast, as most of the positron-emitting nuclei are produced by a (3)He beam in target fragmentation reactions, the calculated total beta(+)-activity during or soon after the irradiation period is evenly distributed within the projectile range. However, we predict also the presence of (13)N, (14)O, (17,18)F created in charge-transfer reactions by low-energy (3)He ions close to the end of their range in several tissue-like media. The time evolution of beta(+)-activity profiles was investigated for both kinds of beams. We found that due to the production of (18)F nuclides the beta(+)-activity profile measured 2 or 3 h after irradiation with (3)He ions will have a distinct peak correlated with the maximum of depth-dose distribution. We also found certain advantages of low-energy (3)He beams over low-energy proton beams for reliable PET monitoring during particle therapy of shallow-located tumours. In this case the distal edge of beta(+)-activity distribution from (17)F nuclei clearly marks the range of (3)He in tissues.

Distributions of positron-emitting nuclei in proton and carbon-ion therapy studied with GEANT4.

Depth distributions of positron-emitting nuclei in PMMA phantoms are calculated within a Monte Carlo model for heavy-ion therapy (MCHIT) based on the GEANT4 toolkit (version 8.0). The calculated total production rates of (11)C, (10)C and (15)O nuclei are compared with experimental data and with corresponding results of the FLUKA and POSGEN codes. The distributions of e(+) annihilation points are obtained by simulating radioactive decay of unstable nuclei and transporting positrons in the surrounding medium. A finite spatial resolution of the positron emission tomography (PET) is taken into account in a simplified way. Depth distributions of beta(+)-activity as seen by a PET scanner are calculated and compared to available data for PMMA phantoms. The obtained beta(+)-activity profiles are in good agreement with PET data for proton and (12)C beams at energies suitable for particle therapy. The MCHIT capability to predict the beta(+)-activity and dose distributions in tissue-like materials of different chemical composition is demonstrated.

Neutrons from fragmentation of light nuclei in tissue-like media: a study with the GEANT4 toolkit.

We study energy deposition by light nuclei in tissue-like media taking into account nuclear fragmentation reactions, in particular, production of secondary neutrons. The calculations are carried out within a Monte Carlo model for heavy-ion therapy (MCHIT) based on the GEANT4 toolkit. Experimental data on depth-dose distributions for 135-400 A MeV (12)C and (18)O beams are described very well without any adjustment of the model parameters. This gives confidence in successful use of the GEANT4 toolkit for MC simulations of cancer therapy with beams of light nuclei. The energy deposition due to secondary neutrons produced by (12)C and (20)Ne beams in a (40-50 cm)(3) water phantom is estimated to be 1-2% of the total dose, that is only slightly above the neutron contribution (approximately 1%) induced by a 200 MeV proton beam.