Physical characterization of3He ion beams for radiotherapy and comparison with4He.

There is increasing interest in using helium ions for radiotherapy, complementary to protons and carbon ions. A large number of patients were treated with4He ions in the US heavy ion therapy project and novel4He ion treatment programs are under preparation, for instance in Germany and Japan.3He ions have been proposed as an alternative to4He ions because the acceleration of3He is technically less difficult than4He. In particular, beam contaminations have been pointed out as a potential safety issue for4He ion beams. This motivated a series of experiments with3He ion beams at Gesellschaft für Schwerionenforschung (GSI), Darmstadt. Measured3He Bragg curves and fragmentation data in water are presented in this work. Those experimental data are compared with FLUKA Monte Carlo simulations. The physical characteristics of3He ion beams are compared to those of4He, for which a large set of data became available in recent years from the preparation work at the Heidelberger Ionenstrahl-Therapiezentrum (HIT). The dose distributions (spread out Bragg peaks, lateral profiles) that can be achieved with3He ions are found to be competitive to4He dose distributions. The effect of beam contaminations on4He depth dose distribution is also addressed. It is concluded that3He ions can be a viable alternative to4He, especially for future compact therapy accelerator designs and upgrades of existing ion therapy facilities.

Intestinal absorption and biliary elimination of glycyrrhizic acid diethyl ester in rats.

BACKGROUND: The purpose of this study was to evaluate absorption and elimination from the gastrointestinal tract of glycyrrhizic acid diethyl ester (GZ-DE) which was prepared as a prodrug of glycyrrhizic acid (a poorly absorbed compound) in rats. METHODS: After the GZ-DE solution was administered via the intravenous, intraduodenal, intraileal, and stomach routes, GZ-DE and GZ concentrations in bile were determined by high-performance liquid chromatography. The stability of GZ-DE was estimated from residual GZ-DE and GZ produced in GZ-DE solutions prepared with distilled water, a pH 1.2 solution, 0.9% NaCl solution, and phosphate-buffered solution (pH 7.4) at 37°C. RESULTS: GZ-DE was eliminated into bile by the pharmacokinetic parameters of apparent distribution rate constant (4.56 ± 0.36 per hour) and apparent elimination rate constant (0.245 ± 0.042 per hour). After intravenous and intraduodenal administration of GZ-DE, the concentration ratio of GZ-DE to GZ in bile was approximately 4:1, and the bioavailability of GZ containing GZ-DE was three-fold higher compared with the bioavailability of GZ after intraduodenal administration. GZ-DE was immediately precipitated in pH 1.2 solution and was converted to GZ by hydrolysis in pH 7.4 solution. CONCLUSION: Improvement of intestinal absorption of GZ was made possible by administration of GZ-DE into the intestine where absorption of GZ is lower than in the strong acidic environment of the stomach. However, because the elimination rate in bile simulated from kinetic parameters of GZ-DE was higher than the conversion rate from GZ-DE to GZ by hydrolysis, it is thought that the availability of GZ as a revolutionary prodrug was not high from the viewpoint of bioavailability of GZ in the liver by intestinal administration of GZ-DE.

[Features of PHITS and its application to medical physics].

PHITS is a general purpose Monte Carlo particle transport simulation code to analyze the transport in three-dimensional phase space and collisions of nearly all particles, including heavy ions, over wide energy range up to 100 GeV/u. Various quantities, such as particle fluence and deposition energies in materials, can be deduced using estimator functions "tally". Recently, a microdosimetric tally function was also developed to apply PHITS to medical physics. Owing to these features, PHITS has been used for medical applications, such as radiation therapy and protection.

Systematic measurement of lineal energy distributions for proton, He and Si ion beams over a wide energy range using a wall-less tissue equivalent proportional counter.

The frequency distributions of the lineal energy, y, of 160 MeV proton, 150 MeV/u helium, and 490 MeV/u silicon ion beams were measured using a wall-less tissue equivalent proportional counter (TEPC) with a site size of 0.72 µm. The measured frequency distributions of y as well as the dose-mean values, y(D), agree with the corresponding data calculated using the microdosimetric function of the particle and heavy ion transport code system PHITS. The values of y(D) increase in the range of LET below ~10 keV µm(-1) because of discrete energy deposition by delta rays, while the relation is reversed above ~10 keV µm(-1) as the amount of energy escaping via delta rays increases. These results indicate that care should be taken with the difference between y(D) and LET when estimating the ionization density that usually relates to relative biological effectiveness (RBE) of energetic heavy ions.

Measurement of microdosimetric spectra with a wall-less tissue-equivalent proportional counter for a 290 MeV/u 12C beam.

The frequency distribution of the lineal energy, y, of a 290 MeV/u carbon beam was measured to obtain the dose-weighted mean of y and compare it with the linear energy transfer (LET). In the experiment, a wall-less tissue-equivalent proportional counter (TEPC) in a cylindrical volume with a simulated diameter of 0.72 microm was used. The measured frequency distribution of y as well as its dose-mean value agrees within 10% uncertainty with the corresponding data from microdosimetric calculations using the PHITS code. The ratio of the measured dose-mean lineal energy to the LET of the 290 MeV/u carbon beam is 0.73, which is much smaller than the corresponding data obtained by a wall TEPC. This result demonstrates that a wall-less TEPC is necessary to precisely measure the dose-mean of y for energetic heavy ion beams.

Calculation of energy-deposition distributions and microdosimetric estimation of the biological effect of a 9C beam.

Among the alternative beams being recently considered for external cancer radiotherapy, (9)C has received some attention because it is expected that its biological effectiveness could be boosted by the beta-delayed emission of two alpha particles and a proton that takes place at the ion-stopping site. Experiments have been performed to characterise this exotic beam physically and models have been developed to estimate quantitatively its biological effect. Here, the particle and heavy-ion transport code system ( PHITS ) is used to calculate energy-deposition and linear energy transfer distributions for a (9)C beam in water and the results are compared with published data. Although PHITS fails to reproduce some of the features of the distributions, it suggests that the decay of (9)C contributes negligibly to the energy-deposition distributions, thus contradicting the previous interpretation of the measured data. We have also performed a microdosimetric calculation to estimate the biological effect of the decay, which was found to be negligible; previous microdosimetric Monte-Carlo calculations were found to be incorrect. An analytical argument, of geometrical nature, confirms this conclusion and gives a theoretical upper bound on the additional biological effectiveness of the decay. However, no explanation can be offered at present for the observed difference in the biological effectiveness between (9)C and (12)C; the reproducibility of this surprising result will be verified in coming experiments.

Glycyrrhizin induces apoptosis in human stomach cancer KATO III and human promyelotic leukemia HL-60 cells.

We have investigated the effects of glycyrrhizin (GL) on cell proliferations of human stomach cancer KATO III and promyelotic leukemia HL-60 cells, and on DNA of those cell lines. GL displayed growth inhibitory effect against KATO III and HL-60 cells. Morphological change showing apoptotic bodies was observed in the KATO III and HL-60 cells treated with GL. The fragmentation of DNA by GL to oligonucleosomal-sized fragments that is a characteristic of apoptosis was observed to be concentration- and time-dependent in both cell lines. Caspase inhibitors such as Z-VAD-FMK and Z-Asp-CH2-DCB suppressed the DNA fragmentation induced by GL. The data of the present study show that the suppression of KATO III and HL-60 cell-growth by GL results from the induction of apoptosis by GL, and that caspase is involved in the induction of apoptosis by GL in these cells.

Sample preparation for routine high-performance liquid chromatographic determination of retinol palmitate in emulsified nutritional supplements by solid-phase extraction using monosodium L-glutamate as dissolving agent.

Retinol palmitate (vitamin A, 73.3 microg/g) in an emulsified nutritional supplement was determined by solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) with fluorescence detection (excitation 350 nm, emission 480 nm) using monosodium L-glutamate as a dissolving agent to obtain higher recovery of vitamin A from the emulsified sample solution. A Bond Elut C2 cartridge (500 mg) was chosen for SPE after comparison with 16 other types. A sample solution was applied to a conditioned Bond Elut C2 cartridge and then vitamin A was eluted with ethanol followed by HPLC. The proposed method was simple, rapid (sample preparation time by SPE: ca. 8 min, retention time: ca. 8 min), sensitive [detection limit: ca. 0.1 pg/injection (100 microl) at a signal-to-noise ratio of 3:1], highly selective and reproducible (relative standard deviation (RSD): ca. 2.9% (n = 5), between-day RSD ca. 3.7 (5 days). The recovery of vitamin A was over 90% by the standard addition method.

Routine high-performance liquid chromatographic determination of ascorbic acid in foods using L-methionine for the pre-analysis sample stabilization.

The possibility of use of phosphoric acid (0.2% v/v, pH 2.1) in the mobile phase and co-existing compounds present in foods as the dissolving agent for the pre-analysis sample stabilization were examined for the routine determination of ascorbic acid (AA) in foods by high-performance liquid chromatography (HPLC) with electrochemical detection (ED). The applied potential was set at 400 mV versus an Ag/AgCl reference electrode. It was demonstrated that 0.2% v/v phosphoric acid was the useful mobile phase and L-methionine was the most effective dissolving agent for the pre-run sample stabilization of AA in foods after comparison with other amino acids and water-soluble vitamins. The proposed method was simple, rapid (retention time @ ca. 4 min), sensitive (detection limit: ca. 0.1 ng per injection (5 microl) at a signal-to-noise ratio of 3), highly selective and reproducible (relative standard deviation (R.S.D.); 2.5% (n=7), between-day R.S.D.: 3.7% (5 days)). The calibration graph of AA was linear in the range of 0.1-12.5 ng per injection (5 microl). Recovery of AA was over 90% by the standard addition method. Relationship between structure of compounds and the stability of AA was also examined.