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PubMedDate not supplied

High-LET pion dose contours under the LAMPF biomedical channel by plastic track detector scanning.

Cellulose-nitrate plastic track detectors have been tested as high spatial-resolution dosimeters at the Biomedical Channel of the Clinton P. Anderson Meson Physics Facility (LAMPF) at the Los Alamos Scientific Laboratory during pilot clinical trials with negative pi mesons (pions). Six plots of dose contours are presented. Reliable macrodosimetry with track detectors would in principle require detector calibration for the particular conditions of geometry and beam parameters in every case but it is interesting that absolute dose values, estimated from data taken with a quite different calibration geometry, were within 20% of agreement with dose values obtained by electronic dosimetry methods. The track detectors measure only the high linear energy transfer (LET) components produced by the pion beam; it is these components which are of special interest in the negative-pion therapy program. Plastic track detectors appear to have many favorable properties for pion dosimetry.

Elementary Particles↗

PubMedDate not supplied

Neutron dose equivalent next to the target shield of a neutron therapy facility using an LET counter.

The use of a spherical tissue-equivalent proportional counter for measurements of the lineal energy (y) and derivations of the linear energy transfer (LET) for fast neutrons has the advantage of giving distributions of dose and dose equivalent as functions of either LET or y. A measurement next to the target shielding of the neutron therapy facility at the University of Chicago Hospitals and Clinics (UCHC) is described, and the data processing is outlined. The distributions are presented and compared to those from measurements in the neutron beam. The average quality factors are presented.

Energy Transfer↗

PubMedDate not supplied

On-line characterization of heavy-ion beams with semiconductor detectors.

Heavy-ion beams used in biomedical studies suffer a substantial amount of nuclear reactions (fragmentation) as they traverse matter. Since it has been demonstrated that dose and linear energy transfer (LET) are not a sufficient description of a beam for the purpose of understanding its biological effects, it is necessary to be able to separate the components of a complex beam so that their individual effects can be analyzed. A simple and small assembly consisting of a thin silicon LET detector, in time coincidence with a thick germanium residual energy detector has been used in measurements of the components of Ne-20 and Si-28 high-energy ion beams. The detector system can be placed at any experimental area without difficulty and it can carry out a beam analysis in a few minutes, making it very appropriate for fast on-line measurements and verification of beam characteristics. LET values measured by the silicon detector agree well with results of the Bethe stopping-power calculations, and the dose measured for the beam components can be used to obtain Bragg curves that are in good agreement with those obtained by ionization chamber measurements on the same beams. The numbers and LET distribution of primaries and fragments at different positions of the Bragg curves, as well as fractional dose contributed by the different components are determined directly from the experimental data. Particle velocity distributions can be obtained for the higher Z fragments. Limitations and advantages of the simple measurement technique are discussed.

Energy Transfer↗

PubMedDate not supplied

Radiation quality investigations around a neutron therapy beam, using a high-pressure ionization chamber.

The mean quality factor (Q) and the dose mean linear energy transfer [LET (LD)] a few centimeters outside a neutron therapy beam have been measured using a high-pressure ionization chamber. Measurements have been carried out in air, 5 and 100 cm outside the treatment field edge on the patient plane for p(46)-Be neurons and are compared with the results obtained at the same points with a low-pressure proportional counter (Rossi counter) and a Bonner spheres system. General agreement is found between these independent methods. The dose equivalent at 5 and 100 cm distances outside the field edge is 2% and 0.4% of the dose equivalent at the isocenter. Measurements were also performed at the same points as a function of proton energy on the Be target. Proton energies of 25-46 MeV on Be were applied. The results indicate increase in the mean quality factor at proton energies below 30 MeV.

Humans↗

PubMedDate not supplied

Characterization of fragmented heavy-ion beams using a three-stage telescope detector: measurements of 670-MeV/amu 20Ne beams.

Measurements of a 670-MeV/amu 20Ne beam at the Lawrence Berkeley Laboratory Bevalac heavy-ion accelerator with various thicknesses of water absorber were obtained with the BERKLET. The BERKLET, a simple three-stage solid-state telescope detector, has been described previously. This instrument measures the linear energy transfer (LET) and residual energy of particles, allows the identification of the particle's charge, and provides a means of obtaining LET and energy statistics for the beam, separated by particle charge. The track and dose averaged LET dependence on the amount of water absorber was determined for each species of fragment in the beam. Large numbers of low-LET particles in the fragmented beam were detected. The results of the analysis are presented followed by a discussion of the effects of multiple scattering and secondary fragmentation on the measurements. A brief discussion of the implications of the BERKLET measurements for radiobiology is also presented.

Energy Transfer↗

PubMedDate not supplied

Characterization of fragmented heavy-ion beams using a three-stage telescope detector: detector configuration and instrumentation.

Accelerated heavy-ion beams used in biological and medical research are often utilized in conjunction with absorbers which lead to the fragmentation of the beam. The BERKLET, initially a two-stage solid-state telescope detector, was designed to make rapid, on-line energy and linear energy transfer (LET) measurements of individual particles in a heavy-ion beam, thus allowing characterization of fragmented beams. From data collected with the BERKLET, one is able to determine a number of important parameters. These include: residual energy and LET histograms for the full beam and for the individual Z components, relative number of particles with a given Z, and dose and track average LET's for the full beam and for the individual Z's. Improvements to the BERKLET design and changes in data analysis are discussed and contrasted with the results of an earlier BERKLET configuration. The most notable improvements are the addition of a thin scintillation detector for improved LET measurement, a tenfold improvement in the dynamic range of the event discriminator, reported here as 1:2000, and dual high-and low-gain amplification of the LET signals, permitting the identification of particles with Z's ranging from 12 down to 1.

Energy Transfer↗

PubMedDate not supplied

Pressure wave generated by the passage of a heavy charged particle in water.

Energy deposition around the trajectories of ionizing particles with linear energy transfer (LET) of 4, 40, and 400 keV/microns in water and subsequent diffusion of deposited heat is calculated using computational fluid dynamics. Immediately after the deposition of energy by the charged particle, the temperature and pressure in the vicinity of the particle track both increase dramatically, leading to the formation of a thermal spike and a pressure wave. Initially, the region of heat deposition is primarily localized to a region called the "thermal core," which has dimensions of 0.3, 1, and 3 nm for particles with LETs of 4, 40, and 400 keV/microns, respectively. Instantaneous peak temperatures within the thermal core were 800 degrees C-2000 degrees C and peak pressures were about 25,000 atm. This sudden deposition of heat in a localized region leads to a very strong shock wave around the particle trajectory, which is shown to last for a duration of 10(-9)-10(-8) s. Even at distances beyond 10 nm away from the particle trajectory, pressures above 100 atm could exist for a duration of up to 10(-11) s. This local and transient environment, created by the passage of a charged particle in a medium, may lead to new mechanisms of radiation action leading to cell damage, as well as to the development of new radiation detectors.

Energy Transfer↗

PubMed1994

Dosimetry of Auger-electron-emitting radionuclides: report no. 3 of AAPM Nuclear Medicine Task Group No. 6.

The biological effects of Auger-electron-emitting radionuclides can be as severe as those of alpha particles of high linear energy transfer. A great deal of effort has been expended in exploring the biological effects of Auger electron emitters. Much of this effort has been devoted to improving theoretical and experimental techniques required to calculate absorbed doses and correlate them with the observed biological effects. Given that the main purpose of dosimetry is to obtain a physical descriptor with which to correlate radiation toxicity, then nowhere is this challenge greater than when biological specimens are subject to Auger electron cascades. The dense shower of short-range Auger electrons released by radionuclides, which decay by electron capture or internal conversion, results in biological damage that is highly dependent on the location of the decay site within the cell. In this report, different approaches to Auger electron dosimetry are described and compared. Methods to calculate the absorbed dose from Auger electron emitters at the DNA, cellular, multicellular, and organ levels are described as they relate to the biological effects. The concept of a radiation weighting factor for Auger electrons to be used in the calculation of equivalent dose is reviewed. The importance of subcellular distribution of Auger emitters in determining the biological effects of these radionuclides is emphasized and incorporated into the equivalent dose formalism. The Task Group recommends that a preliminary radiation weighting factor of 10 be used for deterministic effects of Auger electrons, and a value of 20 for stochastic effects.

Biophysical Phenomena↗

PubMed1988

Radioimmunotherapy with alpha-particle-emitting immunoconjugates.

Alpha particles are energetic short-range ions whose higher linear energy transfer produces extreme cytotoxicity. An alpha-particle-emitting radioimmunoconjugate consisting of a bismuth-212-labeled monoclonal immunoglobulin M specific for the murine T cell/neuroectodermal surface antigen Thy 1.2 was prepared. Analysis in vitro showed that the radioimmunoconjugate was selectively cytotoxic to a Thy 1.2+ EL-4 murine tumor cell line. Approximately three bismuth-212-labeled immunoconjugates per target cell reduced the uptake of [3H]thymidine by the EL-4 target cells to background levels. Mice inoculated intraperitoneally with EL-4 cells were cured of their ascites after intraperitoneal injection of 150 microcuries of the antigen-specific radioimmunoconjugate, suggesting a possible role for such conjugates in intracavitary cancer therapy.

Alpha Particles↗

PubMed1987

Fallout, radiation doses near Dounreay, and childhood leukaemia.

Possible explanations for the recently reported increased incidence of childhood leukaemia around Dounreay were examined in the light of changes in the national incidence of leukaemia that occurred during the period of exposure to fallout from international testing of nuclear weapons in the atmosphere. It was concluded that the increase could not be accounted for by an underestimate of the risk of leukaemia per unit dose of radiation at low doses and low dose rates, nor by an underestimate of the relative biological efficiency of high as compared with low linear energy transfer radiation. One possible explanation was underestimation of doses to the red bone marrow due to the discharges at Dounreay relative to the dose from fallout, though investigation of ways in which this might have occurred did not suggest anything definite. Other possible explanations included a misconception of the site of origin of childhood leukaemia, outbreaks of an infectious disease, and exposure to some other, unidentified environmental agent. These findings weigh heavily against the hypothesis that the recent increase in childhood leukaemia near Dounreay might be accounted for by radioactive discharges from nuclear plants, unless the doses to the stem cells from which childhood leukaemia originates have been grossly underestimated.

Adolescent↗

PubMed2002

Effect of pre-exposure to beta rays of tritium on some biochemical parameters measured in organs of rats subsequently irradiated with fast neutrons.

The experiment examined biological responses produced by combined sequential exposure to low-level tritium contamination, followed by challenging irradiation with fast neutrons. Modifications of endogenous antioxidant potential of different organs in rats were discussed in relation to tissue radiosensitivity. Rats pre-contaminated to 7 cGy and 35 cGy have been additionally irradiated to 1 Gy with fast neutrons. Lipid peroxide level was determined in liver, kidney, small intestine, spleen, bone marrow, and plasma. Reduced glutathione (GSH) level and glucose-6-phosphate dehydrogenase (G6PDH) activity were determined in erythrocytes. An in vitro thymidine uptake assay was performed in isolated bone marrow cells. The lipid peroxide level decreased significantly only in liver and kidney from rats pre-exposed to 35 cGy. For small intestine and spleen, tissues of comparatively higher radiosensitivity, no induced radioprotection was observed, as reflected in the homeostasis of the lipid peroxides. The same behavior was observed in bone marrow, the most radiosensitive tissue studied. However, the bone marrow thymidine-incorporation assay revealed a possible adaptive-type reaction in rats pre-exposed to 35 cGy. We conclude that for radiosensitive tissues pre-exposure to chronic low doses of low linear energy transfer (LET) irradiation has no protective effect on their antioxidant status, whereas a protective effect is observed in radioresistent tissues.

Adaptation, Physiological↗

PubMed2004

Cisplatin enhances the cytotoxicity of fast neutrons in a murine lymphoma cell line.

The utilization of high linear energy transfer (LET) radiations, such as fast neutrons or carbon ions (hadrontherapy), offers promising perspectives in radiotherapy. While it is well known that by combining radiotherapy and chemotherapy, important therapeutic advantages can be obtained to cure cancer, there have been, so far, very few investigations on the effects of treatments combining an irradiation with high-LET particles and cancer drugs. The present study was therefore undertaken to examine the effects of exposure to 65 MeV fast neutrons combined with cisplatin in a murine T cell lymphoma (RDM4) in vitro. The cells were irradiated at doses ranging from 2 to 8 Gy without or with addition of cisplatin shortly before the irradiation, at concentrations between 0.3 and 12.5 micro M. These treatments were applied concomitantly. Proliferation and apoptosis were assessed at different time intervals thereafter. The combination of irradiation with cisplatin was found to be more cytotoxic than either treatment alone. Furthermore, the cytotoxicity induced by this cotreatment resulted not only from apoptosis but also from other forms of cell death.

Animals↗

PubMed1975

Microdosimetry of negative poins at LAMPF.

Lineal energy distributions and linear energy transfer (LET) spectra are being measured at the biomedical facility of the Los Alamos Scientific Laboratory for a negative pion beam having an initial momentum of 168 MeV/c. The results show that the fraction of the dose for lineal energies greater than 50 keV/mum is approximately 2% in the plateau and approximately 12% at the Bragg peak. Preliminary data indicate that the high lineal energy (and high LET) component increases significantly in the region slightly downstream from the peak.

Elementary Particles↗

PubMed1975

The response of a human malignant melanoma cell line to high LET radiation.

The response of a human malignant melanoma cell line in vitro to high linear energy transfer radiation was studied utilizing the neutrons produced by the reaction of 16 and 50 MeV deuterons on beryllium. The relative biological effectiveness (RBE) relative to cobalt-60 gamma radiation was determined under conditions of complete oxygenation. The data indicate that the radioresistance ascribed to malignant melanoma in vivo is not an intrinsic quality of the cell but rather may be mediated by the in vivo environment.

Animals↗

PubMed1976

A fast neutron source for cultured cell irradiation.

Because of recent interest in the use of neutrons for radiotherapy, there has been an increased interest in the radiology of neutrons. In this irradiated cell study, a 1.3 MeV accelerator produced beam currents over 100 muA on the water-cooled 3-mm thick beryllium disk target. The monolayer of irradiated cells was neutron-shielded by about 700 kg of paraffin. The neutron energy spectrum for the 9Be(d,n)10B reaction was obtained, with an average neutron energy calculated to be between 3.3 and 3.5 MeV, and an average linear energy transfer calculated at more than 30 keV/micron.

Cells, Cultured↗

PubMed1978

The three dose components of negative pion beam and their role in pion radiotherapy.

A new method has been developed for analyzing therapeutic negative pion beams into three LET (linear energy transfer) dose components inherent in such a beam. The technique utilizes thin silicon detectors to obtain pulse height spectra produced by the various particles in the beam traversing the detectors. It is shown that a low LET group is correlated with the incoming pions, muons and electrons; a medium LET group corresponds to protons, deuterons, tritons, and high energy alpha particles; and a high LET group is due to low energy alpha particles, 3He and recoil particles. Several beams used clinically have been studied.

Energy Transfer↗

PubMed1980

Scheduling of hypoxic-tumor therapy using neutron brachytherapy.

Fast-neutron-beam therapy and low-dose-rate fast-neutron intracavitary therapy of cervical carcinoma are effective in producing regression of advanced tumors. However, effectiveness is critically dependent on the schedule by which they are used in combination with fractionated external low-linear-energy-transfer (LET) therapy. Neutron-beam therapy is now alternated frequently with fractionated external radiotherapy (mixed beam). Intracavitary neutron therapy, scheduled before fractionated external-beam photon therapy, was maximally effective. These findings indicate that traditional concepts developed for the use of conventional low-LET therapy may need to be altered to use neutrons for therapy and to achieve improved local control of advanced cancers.

Brachytherapy↗

PubMed2005

Chromosomal instability in unirradiated hemopoietic cells resulting from a delayed in vivo bystander effect of gamma radiation.

Untargeted effects of ionizing radiation (de novo effects in the unirradiated descendants or neighbors of irradiated cells) challenge widely held views about the mechanisms of radiation-induced DNA damage with implications for the health consequences of radiation exposures particularly in the context of the induction of malignancy. To investigate in vivo untargeted effects of sparsely ionizing (low linear energy transfer) radiation, a congenic sex-mismatch bone marrow transplantation protocol has been used to repopulate the hemopoietic system from a mixture of gamma-irradiated and nonirradiated hemopoietic stem cells such that host-, irradiated donor- and unirradiated donor-derived cells can be distinguished. Chromosomal instability in the progeny of irradiated hemopoietic stem cells accompanied by a reduction in their contribution to the repopulated hemopoietic system is consistent with a delayed genomic instability phenotype being expressed in vivo. However, chromosomal instability was also shown in the progeny of the nonirradiated hemopoietic stem cells implicating a bystander mechanism. Studies of the influence of irradiated recipient stromal microenvironment and experiments replacing irradiated cells with irradiated cell-conditioned medium reveal the source of the in vivo bystander effect to be the descendants of irradiated cells, rather than irradiated cell themselves. Thus, it is possible that a radiation-induced genomic instability phenotype in vivo need not necessarily be a reflection of intrinsically unstable cells but the responses to ongoing production of inflammatory-type damaging signals as a long-term unexpected consequence of the initial single radiation exposure.

Animals↗