A critical analysis of the use of radiation inactivation to measure the mass of protein.

Measurements are presented of the radiation inactivation of four enzymes exposed to a 6 MeV proton beam. It has long been thought that the measurement of the susceptibility of an enzyme to ionizing radiation can be used to determine its molecular mass. Results are frequently interpreted using the empirical analysis of Kempner and Macey (Biochim. Biophys. Acta 163, 188-203, 1963). We examine this analysis and discuss the validity and limitations of the assumptions on which it is based. Our results indicate that the specific biochemical properties of each enzyme make a significant contribution to its radiation sensitivity.

What is the best proton energy for accelerator-based BNCT using the 7Li(p,n)7Be reaction?

With a growing interest in the use of accelerator-based epithermal neutron sources for BNCT programs, in particular those based upon the 7Li(p,n)7Be reaction, there is a need to address the question of "what is the best proton energy to use?" This paper considers this question by using radiation transport calculations to investigate a range of proton energies from 2.15 to 3.5 MeV and a range of moderator sizes. This study has moved away completely from the use of empty therapy beam parameters and instead defines the beam quality and optimizes the moderator design using widely accepted in-phantom treatment planning figures of merit. It is concluded that up to a proton energy of about 2.8 MeV there is no observed variation in the achievable therapy beam quality, but a price is paid in terms of treatment time for not choosing the upper limit of this range. For higher proton energies, the beam quality falls, but with no improvement in treatment time for optimum configurations.

Design for an accelerator-based orthogonal epithermal neutron beam for boron neutron capture therapy.

This paper is concerned with the proposed Birmingham accelerator-based epithermal neutron beam for boron neutron capture therapy (BNCT). In particular, the option of producing a therapy beam at an orthogonal direction to the incoming protons is considered. Monte Carlo radiation transport simulations, both with and without a head phantom, have shown that an orthogonal beam geometry is not only acceptable but is indeed beneficial, in terms of a lower mean neutron energy and an enhanced therapeutic ratio for the same useful neutron fluence in the therapy beam. Typical treatment times for various beam options have been calculated, and range from 20 to 48 min with a 5 mA beam of 2.8 MeV protons, if the maximum photon-equivalent dose delivered to healthy tissue is to be 12.6 Gy Eq. The effects of proton beam diameter upon the therapy beam parameters have also been considered.

Use of low-pressure tissue equivalent proportional counters for the dosimetry of neutron beams used in BNCT and BNCEFNT.

The absorbed dose in a phantom or patient in boron neutron capture therapy (BNCT) and boron neutron capture enhanced fast neutron therapy (BNCEFNT) is deposited by gamma rays, neutrons of a range of energies and the 10B reaction products. These dose components are commonly measured with paired (TE/Mg) ion chambers and foil activation technique. In the present work, we have investigated the use of paired tissue equivalent (TE) and TE+ l0B proportional counters as an alternate and complementary dosimetry technique for use in these neutron beams. We first describe various aspects of counter operation, uncertainties in dose measurement, and interpretation of the data. We then present measurements made in the following radiation fields: An epithermal beam at the University of Birmingham in the United Kingdom, a d(48.5) + Be fast neutron therapy beam at Harper Hospital in Detroit, and a 252Cf radiation field. In the epithermal beam, our measured gamma and neutron dose rates compare very well with the values calculated using Monte Carlo methods. The measured 10B dose rates show a systematic difference of approximately 35% when compared to the calculations. The measured neutron+gamma dose rates in the fast neutron beam are in good agreement with those measured using a calibrated A-150 TEP (tissue equivalent plastic) ion chamber. The measured 10B dose rates compare very well with those measured using other methods. In the 252Cf radiation field, the measured dose rates for all three components agree well with other Monte Carlo calculations and measurements. Based on these results, we conclude that the paired low-pressure proportional counters can be used to establish an independent technique of dose measurement in these radiation fields.

Toward a final design for the Birmingham boron neutron capture therapy neutron beam.

This paper is concerned with the proposed Birmingham accelerator-based epithermal neutron beam for boron neutron capture therapy (BNCT). Details of the final moderator design, such as beam delimiter, shield, and beam exit surface shape are considered. Monte Carlo radiation transport simulations with a head and body phantom have shown that a simple flat moderator beam exit surface is preferable to the previously envisioned spherical design. Dose rates to individual body organs during treatment have been calculated using a standard MIRD phantom. We have shown that a simple polyethylene shield, doped with natural lithium, is sufficient to provide adequate protection to the rest of the body during head irradiations. The effect upon the head phantom dose distributions of the use of such a shield to delimit the therapy beam has been evaluated.

In-phantom neutron fluence measurements in the orthogonal Birmingham boron neutron capture therapy beam.

This paper presents the results of an experimental investigation into the performance of the Birmingham accelerator-based epithermal BNCT beam. In-phantom gold foil activation and boron trifluoride tube measurements have been used. The results have been compared with calculated response rates using Monte Carlo modeling of the entire neutron system from source to phantom and detector. The excellent agreement obtained gives us confidence in the validity of the simulations and our ability to predict accurately the neutronic performance of our BNCT facility.

A design study for an accelerator-based epithermal neutron beam for BNCT.

An achievable design concept for a boron neutron capture therapy (BNCT) facility, based on a high-current, low-energy proton accelerator, is described. Neutrons are produced within a thick natural lithium target, under bombardment from protons with an initial energy between 2.5 and 3.0 MeV. The proton current will be up to 10 mA. After gamma-ray filtering, the neutrons are partially moderated to epithermal energies within a heavy-water moderator, poisoned with 6Li to remove thermal neutrons. Monte Carlo modelling has been used to predict system performance in terms of neutron fluence rate and neutron and gamma-ray dose at the patient position. The relationship between the system performance and key parameters, such as proton energy, moderator depth and 6Li concentration, has been investigated. With a proton current of 10 mA, the facility is capable of providing a therapy beam with a useful neutron fluence rate of 10(9) cm-2 s-1 and a neutron dose per unit fluence of less than 6 x 10(-13) Gy cm2, with a gamma-ray contamination of the therapy beam of about 10(-13) Gy cm2.

Computational study of diffraction patterns for near-field Fresnel and Gabor zone plates.

Near-field designs of Fresnel and Gabor zone plates are computationally analyzed by using versions that allow the foci to be brought closer to the plate than in the usual far-field applications. It is found that the Fresnel plate has a dominant primary conjugate pair of foci well inside the far-field region and a more intense primary focus and smaller off-focal-plane sidelobes than the near-field Gabor systems, thus yielding a superior imaging performance.

Gabor zone plate with binary transmittance values.

A methodology is presented for producing a Gabor zone plate by using a binary transmittance function that is both radially and azimuthally distributed on the surface of the plate. The measured optical properties of such a plate are shown to be in agreement with those of the idealized Gabor plate that possesses a radially sinusoidal transmittance function.

Modulation of firefly luciferase bioluminescence at bioelectrochemical interfaces.

This paper describes a method by which the activity of an immobilized enzyme can be modulated electrochemically at an electrode. The particular example studied, involving the enzyme firefly luciferase being immobilized in a gelatin film of thickness <1 µm, provides a useful model system since changes in the catalytic activity can be measured instantaneously through the natural bioluminescent emission. Using this biointerfacial arrangement, we have been able to demonstrate the reversible switching off and on of the enzyme's activity. Through a series of mechanistic studies, we have been able to determine that the bioluminescence response is modulated (on long time scales) as a consequence of the electrochemical depletion of protons at the electrode interface resulting in a local increase in pH.