Heavy-ion conformal irradiation in the shallow-seated tumor therapy terminal at HIRFL

Basic research related to heavy-ion cancer therapy has been done at the Institute of Modern Physics (IMP), Chinese Academy of Sciences since 1995. Now a plan of clinical trial with heavy ions has been launched at IMP. First, superficially placed tumor treatment with heavy ions is expected in the therapy terminal at the Heavy Ion Research Facility in Lanzhou (HIRFL), where carbon ion beams with energy up to 100 MeV/u can be supplied. The shallow-seated tumor therapy terminal at HIRFL is equipped with a passive beam delivery system including two orthogonal dipole magnets, which continuously scan pencil beams laterally and generate a broad and uniform irradiation field, a motor-driven energy degrader and a multi-leaf collimator. Two different types of range modulator, ripple filter and ridge filter with which Guassian-shaped physical dose and uniform biological effective dose Bragg peaks can be shaped for therapeutic ion beams respectively, have been designed and manufactured. Therefore, two-dimensional and three-dimensional conformal irradiations to tumors can be performed with the passive beam delivery system at the earlier therapy terminal. Both the conformal irradiation methods have been verified experimentally and carbon-ion conformal irradiations to patients with superficially placed tumors have been carried out at HIRFL since November 2006.

Probing the medium effect and isospin dependence of the in-medium nucleon-nucleon cross section in heavy ion collisions

Probing in-medium nucleon-nucleon (NN) cross section sigma(1)(NN)(alpha) in heavy ion collisions has been investigated by means of the isospin-dependent quantum molecular dynamics (IQMD) with the isospin- and momentum- dependent interaction (IMDI(tau)). It is found that there are the very obvious medium effect and the sensitive isospin- dependence of nuclear stopping R on the in-medium NN cross section sigma(1)(NN)(alpha) in the nuclear reactions induced by halo-neutron projectile and the same-mass stable projectile. However, R induced by the neutron-halo projectile is obviously lower than that induced by the corresponding stable projectile. In particular, there is a very obvious dependence of R on the medium effect of sigma(1)(NN)(alpha) in the whole beam energy region for the above two kinds of projectiles. Therefore, the comparison between the results of R's in the reactions induced by the neutron-halo projectile and the corresponding same-mass stable projectile is a more favourable probe for extracting the information of sigma(1)(NN)(alpha) because of adding a new judgement.

Study on the apoptosis and Bcl-2/Bax expression of human hepatoma SMMC-7721 cells after exposure to heavy-ion and X-ray irradiations

This study is aimed at observing the apoptosis and Bcl-2/Bax gene expression of mammalian cells following heavy-ion and X-ray irradiations. Exponentially growing human hepatoma SMMC-7721 cells cultured in vitro were irradiated with a C-12 ion beam of 50 MeV/u (corresponding to a LET value of 44.56 keV/mu m) from Heavy Ion Research Facility in Lanzhou (HIRFL) at doses varying from 0 to 3 Gy. The X-ray irradiation (8 MV) was performed in the therapy unit of the General Hospital of the Lanzhou Military Area. Survival fractions of irradiated cells at various doses were measured by means of MTT assay. Apoptotic cells after irradiation were analyzed with fluorescence microscope and flow cytometer (FCM). Immuno-histological assay were applied to detect the expression of Bcl-2/Bax genes in the irradiated cells. The survival fraction of SMMC-7721 cells decreased gradually (vs. control p<0.05) with increasing the dose of the carbon ion beam more obviously than X-ray irradiation, and the carbon ion irradiation efficiently induced cell apoptosis and significantly promoted the expression of Bax gene while Bcl-2 gene expression was restrained. High-LET heavy ion beam would induce cell apoptosis effectively than low-LET X-ray, and the apoptosis rate is correlated with the transcription of Bcl-2/Bax and the ratio of Bcl-2/Bax in human hepatoma SMMC-7721 cells after irradiation to heavy ion beam.

Intrabeam scattering of heavy ions at HIRFL-CSR

Small-angle multiple intrabeam scattering (IBS) is an important effect for heavy-ion storage rings with electron cooling, because the cooling time is determined by the equilibrium between cooling and IBS process. All usually used numerical algorithms of IBS growth rate calculations are based on the model of the collisions proposed by A.Piwinski, but this result is a multidimensional integral. In this paper, the IBS growth rates are simulated for HIRFL-CSR using symmetric elliptic integral method, and compared with several available IBS code results.

Nuclear potential and fusion cross sections for synthesizing super-heavy elements in di-nuclear systems

A double folding method with simplified Skyreme-type nucleon-nucleon interaction is used to calculate the nuclear interaction potential between two nuclei. The calculation is performed in tip-to-tip orientation of the two nuclei if they are deformed. Based on this methods, the potential energy surfaces, the fusion probabilities and the evaporation residue cross sections for some cold fusion reactions leading to super-heavy elements within di-nuclear system model are evaluated. It is indicated that after the improvement, the exponential decreasing systematics of the fusion probability with increasing charge number of projectile on the Pb based target become better and the evaporation residue cross sections are in better agreement with the experimental data.

Studies on advantages of heavy ions in radiotherapy compared with gamma-rays

Hepatoma and melanoma cells were exposed to C-12(6+) beams generated by HIRFL facility and gamma-rays and the cell response was studied by colony assays as well as the analysis of RBE of carbon ions was evolved. The survival curves of cells irradiated by heavy ions were different from those of cells irradiated by gamma-rays. And two kinds of cell showed the obvious discrepancy in response to the photon and ion irradiation. The results showed that heavy ions have special physical properties and mighty potency to kill cell in both single and fractional irradiation meanwhile it can kill tumor cells with high radioresistance more efficiently. When involved in clinical therapy, heavy ions will enhance the therapy efficiency and decrease the suffering of patients because it can impair the repair for sublethal damage of cells which can lead to fewer irradiation fractions.

Damage accumulation in gallium nitride irradiated with various energetic heavy ions

In this work a study of damage production in gallium nitride via elastic collision process (nuclear energy deposition) and inelastic collision process (electronic energy deposition) using various heavy ions is presented. Ordinary low-energy heavy ions (Fe+ and Mo+ ions of 110 keV), swift heavy ions (Pb-208(27+) ions of 1.1 MeV/u) and slow highly-charged heavy ions (Xen+ ions of 180 keV) were employed in the irradiation. Damage accumulation in the GaN crystal films as a function of ion fluence and temperature was studied with RBS-channeling technique, Raman scattering technique, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). For ordinary low-energy heavy ion irradiation, the temperature dependence of damage production is moderate up to about 413 K resulting in amorphization of the damaged layer. Enhanced dynamic annealing of defects dominates at higher temperatures. Correlation of amorphization with material decomposition and nitrogen bubble formation was found. In the irradiation of swift heavy ions, rapid damage accumulation and efficient erosion of the irradiated layer occur at a rather low value of electronic energy deposition (about 1.3 keV/nm(3)),. which also varies with irradiation temperature. In the irradiation of slow highly-charged heavy ions (SHCI), enhanced amorphization and surface erosion due to potential energy deposition of SHCI was found. It is indicated that damage production in GaN is remarkably more sensitive to electronic energy loss via excitation and ionization than to nuclear energy loss via elastic collisions.

Structural modification of C-doped SiO2 induced by swift heavy ion irradiations

Thermally grown amorphous SiO2 samples were implanted at room temperature (RT) with 120 keV C-ions to a dose ranging from 1.0 x 10(16) to 8.6 x 10(17)C ions/cm(2), then irradiated at RT with 950 MeV Pb, 345 or 1754 MeV Xe ions to a fluence in the region from 1.0 x 10(11) to 3.8 x 10(12) ions/cm(2), respectively. The irradiated samples were investigated using micro-FTIR and micro-Raman spectroscopes. It was found that new chemical bonds such as Si-C, C=C(O), C C and Si(C)-O-C bonds formed significantly in the C-doped SiO2 films after heavy ion irradiations. The evolution of Si-O-C bonds and possible mechanism of structural modification in C-doped SiO2 induced by swift heavy ion irradiations were discussed.

Chromatid-type aberrations following irradiation in G0 lymphocytes with heavy ions

We describe a low level of chromatid-type aberrations which included the relatively rare isochromatid/chromatid triradial in peripheral blood lymphocytes that were irradiated, ostensibly in GO, with accelerated heavy C-12 ions. These were produced only at the energies of 69 MeV/n (34.6 keV/ mu m), almost absent at the energy of either 58.6 McV/n (46.07 keV/mu m) or 19.3 MeV/n (97 keV/mu m), nor were they found after low-LET X-rays. Mechanisms potentially responsible for their formation are discussed.

Adenovirus-mediated p53 gene transfer sensitizes hepatocellular carcinoma cells to heavy-ion radiation

Background. The purpose of this study was to investigate whether adenovirus-mediated p53 transfer could sensitize hepatocellular carcinoma to heavy-ion irradiation. Methods. HepG2 cells were preexposed to a C-12(6+) beam, and then infected with replication-deficient adenovirus recombinant vectors containing human wild-type p53 (AdCMV-p53) (C-12(6+) irradiation + AdCMV-p53 infection). The survival fraction was determined by clonogenic assay. The cell cycle, cell apoptosis, and p53 expression were monitored by flow cytometric analysis. Results. p53 expression in C-12(6+) irradiation + AdCMV-p53 infection groups was markedly higher than that in C-12(6+) irradiation only groups (P < 0.05), suggesting that the preexposure to the C-12(6+) beam promoted the expression of exogenous p53 in HepG2 cells infected with AdCMV-p53 only. The G(1)-phase arrest and cell apoptosis in the C-12(6+) irradiation + AdCMV-p53 infection groups were significantly more than those in the C-12(6+) irradiated groups (P < 0.05). The survival fractions of the C-12(6+) irradiation + AdCMV-p53 infection groups decreased by 30%-49% compared with those of the C-12(6+) beam-irradiated only groups (P < 0.05). Conclusions. Adenovirus-mediated p53 gene transfer can promote G(1)-phase arrest and cell apoptosis, thus sensitizing hepatocellular carcinoma cells to heavy-ion irradiation.

Color center formation in alpha-Al2O3 induced by high energy heavy ions

Single crystals of alpha-alumina were irradiated at room temperature with 1.157 (GeVFe)-Fe-56, 1.755 (GeVXe)-Xe-136 and 2.636 (GeVU)-U-238 ions to fluences range from 8.7 x 10(9) to 6 x 10(12) ions/cm(2). Virgin and irradiated samples were investigated by ultraviolet visible absorption measurements. The investigation reveals the presence of various color centers (F, F+, F-2(2+), F-2(+) and F-2 centers) appearing in the irradiated samples. It is found that the ratio of peak absorbance of F-2 to F centers increases with the increase of the atomic numbers of the incident ions from Fe, Xe to U ions, so do the absorbance ratio of F-2(2+) to F+ centers and of large defect cluster to F centers, indicating that larger defect clusters are preferred to be produced under heavier ion irradiation. Largest color center production cross-section was found for the U ion irradiation. The number density of single anion vacancy scales better with the energy deposition through processes of nuclear stopping, indicating that the nuclear energy loss processes determines the production of F-type defects in heavy ion irradiated alpha-alumina.

Correlation between initial chromatid damage and survival of various cell lines exposed to heavy charged particles

The biophysical characteristics of heavy ions make them a rational source of radiation for use in radiotherapy of malignant tumours. Prior to radiotherapy treatment, a therapeutic regimen must be precisely defined, and during this stage information on individual patient radiosensitivity would be of very great medical value. There are various methods to predict radiosensitivity, but some shortfalls are difficult to avoid. The present study investigated the induction of chromatid breaks in five different cell lines, including one normal liver cell line (L02), exposed to carbon ions accelerated by the heavy ion research facility in Lanzhou (HIRFL), using chemically induced premature chromosome condensation (PCC). Previous studies have reported the number of chromatid breaks to be linearly related to the radiation dose, but the relationship between cell survival and chromatid breaks is not clear. The major result of the present study is that cellular radiosensitivity, as measured by D-0, is linearly correlated with the frequency of chromatid breaks per Gy in these five cell lines. We propose that PCC may be applied to predict radiosensitivity of tumour cells exposed to heavy ions.

Flipped symmetry potential in heavy-ion collisions

Within the IBUU transport model, flipping of the symmetry potential in heavy-ion collisions is studied. It is found that there exist flipping of the symmetry potential in the isospin fractionation, the single neutron to proton ratio, the double neutron to proton ratio and the neutron-proton differential flow from lower to higher incident energies. The flipping of the symmetry potential results from the change of the relative magnitude of the hard and soft symmetry energies at lower and higher densities. Future observations of the flipped symmetry potential in experiment will help the study of the density-dependent symmetry energy.

Conformal irradiation to moving targets in heavy ion radiotherapy with raster-scanning beam delivery system: (II) feasibility experiments

Within the framework of the pilot heavy-ion therapy facility at GSI equipped with an active beam delivery system of advanced raster scanning technique, a feasibility study on actively conformal heavy-ion irradiation to moving tumors has been experimentally conducted. Laterally, real-time corrections to the beam scanning parameters by the raster scanner, leading to an active beam tracing, compensate for the lateral motion of a target volume. Longitudinally, a mechanically driven wedge energy degrader (called depth scanner) is applied to adjust the beam energy so as to locate the high-dose Bragg peak of heavy ion beam to the slice under treatment for the moving target volume. It has been experimentally shown that compensations for lateral target motion by the raster scanner and longitudinal target shift by the depth scanner are feasible.

Particle transfer and fusion cross-section for super-heavy nuclei in dinuclear system

Within the dinuclear system (DNS) conception, instead of solving the Fokker-Planck equation (FPE) analytically, the master equation is solved numerically to calculate the fusion probability of super-heavy nuclei, so that the harmonic oscillator approximation to the potential energy of the DNS is avoided. The relative motion concerning the energy, the angular momentum and the fragment deformation relaxations is explicitly treated to couple with the diffusion process. The nucleon transition probabilities, which are derived microscopically, are related with the energy dissipation of the relative motion. Thus they are time dependent. Comparing with the analytical solution of FPE at the equilibrium, our time-dependent results preserve more dynamical effects. The calculated evaporation residue cross-sections for one-neutron emission channel of Pb-based reactions are basically in agreement with the known experimental data within one order of magnitude.