Clinical trials using accelerated heavy charged‐particle beams for treating cancer and other diseases have been performed for nearly four decades. Recently there have been worldwide efforts to construct hospital‐based medically dedicated proton or light‐ion accelerator facilities. To make such accelerated heavy charged‐particle beams clinically useful, specialized instruments must be developed to modify the physical characteristics of the particle beams in order to optimize their biological and clinical effects. This article reviews the beam modifying devices and associated dosimetric equipment developed specifically for controlling and monitoring the clinical beams.

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Instrumentation for Treatment of Cancer Using Proton and Light-Ion Beams

The response of cultured CHO cells to ultrahigh dose rate (approx.10/sup 11/ rad/sec) radiation, as measured by colony-forming ability, was studied under various oxygen concentrations with single electron pulses of 3 nsec duration. A thin-layer technique was designed for these experiments to permit rapid equilibration of the cells with the ambient oxygen-containing gas and to ensure that no segments of the cell population were shielded from the relatively low energy electrons (average energy, approx.450 keV), thus eliminating the possibility of artifacts influencing surviving fraction. Dosimetry was performed using a combination of calorimetric, charge-measuring, and thermoluminescent techniques. At a concentration of 0.44% oxygen, breaking behavior of the survival curve was observed in accord with the radiolytic depletion of intracellular oxygen by the radiation pulse. The sensitivity for doses greater than the breakpoint dose followed an anoxic response, clearly different from that observed when the cells were irradiated at conventional dose rates in the same gas under the identical geometry. The breakpoint dose was found to be approximately linear over the oxygen concentration range 0 to 0.7%. These results are consistent with recent observations of mammalian cell response under high-intensity irradiation conditions and provide a basis for the design of a double-pulsemore » experiment.« less

Oxygen Sensitization of CHO Cells at Ultrahigh Dose Rates: Prelude to Oxygen Diffusion Studies

A consistent method for grouping of catastrophic and noncatastrophic interactions in mixed Monte Carlo schemes has been developed. Energy-loss straggling between discrete catastrophic energy losses is taken into account by sampling from a restricted energy straggling distribution derived from the energy loss theory of Vavilov applied on the interaction cross section of M0ller. Similarly, multiple small-angle scattering interactions between catastrophic large-angle deflections are taken into account by using a restricted scattering power which includes only scattering events smaller than a certain cut-off angle b. This latter approach in particular improves the efficiency and accuracy of calculated spatial distributions as demonstrated by

Restricted Energy-Loss Straggling and Multiple Scattering of Electrons in Mixed Monte Carlo Procedures

: The scientific literature on radiation-protective drugs is reviewed. Emphasis is placed on the mechanisms involved in determining the sensitivity of biological material to ionizing radiation and mechanisms of chemical radioprotection. In Section I, the types of radiation are described and the effects of ionizing radiation on biological systems are reviewed. The effects of ionizing radiation are briefly contrasted with the effects of non-ionizing radiation. Section II reviews the contributions of various natural factors which influence the inherent radiosensitivity of biological systems. Included in the list of these factors are water, oxygen, thiols, vitamins and antioxidants. Brief attention is given to the model describing competition between oxygen and natural radioprotective substances (principally, thiols) in determining the net cellular radiosensitivity. Several theories of the mechanism(s) of action of radioprotective drugs are described in Section III. These mechanisms include the production of hypoxia, detoxication of radiochemical reactive species, stabilization of the radiobiological target and the enhancement of damage repair processes. Section IV describes the current strategies for the treatment of radiation injury. Likely areas in which fruitful research might be performed are described in Section V.

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Chemical Protection against Ionizing Radiation

The oxygen effect in cultured HeLa cells exposed to single short (3 nsec) pulses of electrons from a field emission source has been investigated. Cellular radiosensitivity as measured by the abilit...

The Radiosensitivity of Cultured Mammalian Cells Exposed to Single High Intensity Pulses of Electrons in Various Concentrations of Oxygen

A new upper limit of 1× 10-4 seconds has been measured for thel ifetime of oxygen-dependent chemical species suspected to be induced at critical sites in irradiated bacterial cells. The technique employed involved the delivery of two high-intensity electron pulses to a thin wet layer of bacterial cells surrounded by a known concentration of gaseous oxygen. The pulses were of 3 nsec duration provided by two 600 kV electron sources utilizing the phenomenon of field emission. The first pulse was designed to provide sufficient dose to deplete oxygen completely from within the bacteria by radiation-induced chemical reactions. The second pulse was applied to the cells at an accurately known time interval which was variable throughout the microsecond and millisecond regions. The amount of oxygen rediffused to critical sites within cells during the interpulse time was inferred from the known response of cells to single short pulse irradiations. In this way the diffusion of oxygen in the irradiated cells was measu...

Oxygen Diffusion Times in Bacterial Cells Irradiated with High-Intensity Pulsed Electrons: New Upper Limit to the Lifetime of Oxygen-Sensitive Species Suspected to Be Induced at Critical Sites in Bacterial Cells

Detailed measurements have been made of the dose absorbed by the bone marrow and by the reproductive organs of a realistic human phantom exposed to antero-posterior and lateral radiographic examinations of the pelvis, lumbar spine, thoracic spine and cervical spine, and to the antero-posterior examination of the hip. The measurements were made over a range of parameters including kilovoltage, filtration, and useful beam size. The kilovoltage, range extended, for most of the examinations, from 60 to 110 kVp. The effect of added filtrations of 1 and 2 mm Al was determined for most cases. In general, measurements were made for two X-ray field arrangements. Arrangement A, provided by a well-shielded collimator, yielded a field just large enough to cover the film of interest. Arrangement B was provided by a conventional radiographic cone yielding a field usually considerably larger than the film. The method of measurement involved the use of small ionization chambers which exhibited a high degree of energy, di...

Measurement of Bone Marrow and Gonadal Dose from X-ray Examinations of the Pelvis, Hip and Spine as a Function of Field Size, Tube Kilovoltage and added Filtration

Breaking survival curves have been measured for Serratia marcescens on Millipore filters equilibrated with known oxygen concentrations and irradiated by single pulses at ultrahigh dose rates. This phenomenon is attributed to the radiochemical depletion of intracellular oxygen and provides a basis for double-pulse experiments conducted to measure diffusion of oxygen in irradiated cells. A first pulse with sufficient dose to deplete intracellular oxygen precedes a similar second pulse by an accurately known interpulse time, variable from 10-6 sec to 30 sec. The amount of oxygen diffusing to critical sites in the cell during the interpulse time is inferred by comparison to cellular response measured under various oxygen concentrations with single high-intensity pulses. Oxygen-diffusion curves obtained show that a significant amount of oxygen diffuses to these sites by 10-4 sec. This can be interpreted as an upper limit to the lifetime of the radiation-induced oxygen-dependent damage. This limit is in agreeme...

Irradiation of Serratia marcescens by single and double pulses of high-intensity electrons: oxygen diffusion kinetics and lifetime of oxygen-sensitive species.

The spectrum of the fluence of slowed-down electrons in a water medium irradiated by an external beam of electrons from a betatron has been measured. The measurements were made at a number of depths in the medium and for a number of incident electron energies. The approach used was to set an evacuated probe at the point of interest for a number of angular increments. Electrons traveling down the probe within an angle of θ ± 0.6° were then detected by a plastic scintillator. The measured spectra were corrected for coincidences and resolution distortion by means of a response function matrix. The fluence spectra were converted to distributions in LET.

The Energy Spectrum of Electrons in Water Irradiated with 10- to 20- MeV Electron Beams

WEISS, H., EPP, E. R., AND HESLIN, J. The Energy Spectrum of Electrons in Water Irradiated with 10- to 20-MeV Electron Beams. Radiat. Res. 51, 211-228 (1972). The spectrum of the fluence of slowed-down electrons in a water medium irradiated by an external beam of electrons from a betatron has been measured. The measurements were made at a number of depths in the medium and for a number of incident electron energies. The approach used was to set an evacuated probe at the point of interest for a number of angular increments. Electrons traveling down the probe within an angle of 0 =t 0.60 were then detected by a plastic scintillator. The measured spectra were corrected for coincidences and resolution distortion by means of a response function matrix. The fluence spectra were converted to distributions in LET.

Jane Heslin

Papers

Oxygen Diffusion Times in Bacterial Cells Irradiated with High-Intensity Pulsed Electrons: New Upper Limit to the Lifetime of Oxygen-Sensitive Species Suspected to Be Induced at Critical Sites in Bacterial Cells

Measurement of Bone Marrow and Gonadal Dose from X-ray Examinations of the Pelvis, Hip and Spine as a Function of Field Size, Tube Kilovoltage and added Filtration

Irradiation of Serratia marcescens by single and double pulses of high-intensity electrons: oxygen diffusion kinetics and lifetime of oxygen-sensitive species.

The Energy Spectrum of Electrons in Water Irradiated with 10- to 20- MeV Electron Beams

The Energy Spectrum of Electrons in Water Irradiated with