An investigation of the feasibility of gadolinium for neutron capture synovectomy

Neutron capture synovectomy (NCS) has been proposed as a possible treatment modality for rheumatoid arthritis. Neutron capture synovectomy is a two-part modality, in which a compound containing an isotope with an appreciable thermal neutron capture cross section is injected directly into the joint, followed by irradiation with a neutron beam. Investigations to date for NCS have focused on boron neutron capture synovectomy (BNCS), which utilizes the 10B(n,alpha)7Li nuclear reaction to deliver a highly localized dose to the synovium. This paper examines the feasibility of gadolinium, specifically 157Gd, as an alternative to boron as a neutron capture agent for NCS. This alternative modality is termed Gadolinium Neutron Capture Synovectomy, or GNCS. Monte Carlo simulations have been used to compare 10B and 157Gd as isotopes for accelerator-based NCS. The neutron source used in these calculations was a moderated spectrum from the 9Be(p,n) reaction at a proton energy of 4 MeV. The therapy time to deliver the NCS therapeutic dose of 10000 RBE-cGy, is 27 times longer when 157Gd is used instead of 10B. The skin dose to the treated joint is 33 times larger when 157Gd is used instead of 10B. Furthermore, the impact of using 157Gd instead of 10B was examined in terms of shielded whole-body dose to the patient. The effective dose is 202 mSv for GNCS, compared to 7.6 mSv for BNCS. This is shown to be a result of the longer treatment times required for GNCS; the contribution of the high-energy photons emitted from neutron capture in gadolinium is minimal. Possible explanations as to the relative performance of 157Gd and 10B are discussed, including differences in the RBE and range of boron and gadolinium neutron capture reaction products, and the relative values of the 10B and 157Gd thermal neutron capture cross section as a function of neutron energy.     

Gadolinium as a neutron capture therapy agent.

The clinical results of treating brain tumors with boron neutron capture therapy are very encouraging. Researchers around the world are once again making efforts to develop this therapeutic modality. Gadolinium-157 is one of the nuclides that holds interesting properties of being a neutron capture therapy agent. It is estimated that tumor concentrations of up to 300 micrograms 157 Gd/g tumor can be achieved in brain tumors with some MRI contrast agents such as Gd-DTPA and Gd-DOTA, and up to 800 micrograms 157 Gd/g tumor can be established in bone tumors with Gd-EDTMP. Monte Carlo calculations indicate that with 250 ppm of 157Gd in tumor, neutron capture therapy can deliver 2000 cGy to a tumor of 2-cm diameter or larger with 5 x 10(12) n/cm2 of thermal neutron fluence at the tumor. Dose measurements with films and TLDs in phantoms verified these calculations. More extended Monte Carlo calculations demonstrate that neutron capture therapy with Gd possesses comparable dose distribution to B neutron capture therapy. With 5 x 10(12) n/cm2 thermal neutrons at the tumor, Auger electrons from the Gd produced an optical density enhancement on films that is similar to the effect caused by about 300 cGy of Gd prompt gamma dose and may further enhance the therapeutic effects.     

Boron self-shielding effects on dose delivery of neutron capture therapy using epithermal beam and boronophenylalanine

Previous dosimetry studies for boron neutron capture therapy have often neglected the thermal neutron self-shielding effects caused by the 10B accumulation in the brain and the tumor. The neglect of thermal neutron flux depression, therefore, results in an overestimation of the actual dose delivery. The relevant errors are expected to be more pronounced when boronophenylalanine is used in conjunction with an epithermal neutron beam. In this paper, the boron self-shielding effects are calculated in terms of the thermal neutron flux depression across the brain and the dose delivered to the tumors. The degree of boron self-shielding is indicated by the difference between the thermal neutron fluxes calculated with and without considering a 10B concentration as part of the head phantom composition. The boron self-shielding effect is found to increase with increasing 10B concentrations and penetration depths from the skin. The calculated differences for 10B concentrations of 7.5-30 ppm are 2.3%-8.3% at 2.3 cm depth (depth of the maximum brain dose) and 4.6%-17% at 7.3 cm depth (the center of the brain). The additional self-shielding effects by the 10B concentration in a bulky tumor are investigated for a 3-cm-diam spherical tumor located either near the surface (3.3 cm depth) or at the center of the brain (7.3 cm depth) along the beam centerline. For 45 ppm of 10B in the tumor and 15 ppm of 10B in the brain, the dose delivered to the tumors is approximately 10% lower at 3.3 cm depth and 20% lower at the center of the brain, compared to the dose neglecting the boron self-shielding in transport calculations.     

Teatment planning figures of merit in thermal and epithermal boron neutron capture therapy of brain tumours

The boron neutron capture therapy (BNCT) figures of merit of advantage depth, therapeutic depth, modified advantage depth and maximum therapeutic depth have been studied as functions of 10B tumour to blood ratios and absolute levels. These relationships were examined using the Monte Carlo neutron photon transport code, MCNP, with an ideal 18.4 cm diameter neutron beam incident laterally upon all ellipsoidal neutron photon brain-equivalent model. Mono-energetic beams of 0.025 eV (thermal) and 35 eV (epithermal) were simulated. Increasing the tumour to blood 10B ratio predictably increases all figures of merit. concentration was also shown to have a strong bearing on the figures of merit when low levels were present in the system. This is the result of a non-10B dependent background dose. At higher levels however, the concentration of 10B has a diminishing influence. For boron sulphydryl (BSH), little advantage is gained by extending the blood 10B level beyond 30 ppm, whilst for D,L,-p-boronophenylalanine (BPA) this limit is 10 ppm. To achieve a therapeutic depth of 6 cm (brain mid-line from brain surface) using the thermal beam, a tumour to blood ratio of 25 with 10 ppm 10B in the blood is required for BPA. Similarly, a tumour to blood ratio of 8.5 with 30 ppm blood 10B is required for the maximum therapeutic depth of BSH to reach the brain mid-line. These requirements are five times above current values for these compounds in humans. Applying the epithermal beam under identical conditions, the therapeutic depth reaches the brain mid-line with a tumour to blood 10B ratio of only 5.7 for BPA. For BSH, the maximum therapeutic depth reaches the brain mid-line with a tumour to blood ratio of only 1.9 with 30 ppm in the blood. Human data for these compounds are very close to these requirements.     

The measurement of thermal neutron flux depression for determining the concentration of boron in blood

Boron neutron capture therapy (BNCT) is a form of targeted radiotherapy that relies on the uptake of the capture element boron by the volume to be treated. The treatment procedure requires the measurement of boron in the patient's blood. The investigation of a simple and inexpensive method for determining the concentration of the capture element 10B in blood is described here. This method, neutron flux depression measurement, involves the determination of the flux depression of thermal neutrons as they pass through a boron-containing sample. It is shown via Monte Carlo calculations and experimental verification that, for a maximum count rate of 1 x 10(4) counts/s measured by the detector, a 10 ppm 10B sample of volume 20 ml can be measured with a statistical precision of 10% in 32 +/- 2 min. For a source activity of less than 1.11 x 10(11) Bq and a maximum count rate of less than 1 x 10(4) counts/s, a 10 ppm 10B sample of volume 20 ml can be measured with a statistical precision of 10% in 58 +/- 3 min. It has also been shown that this technique can be applied to the measurement of the concentration of any element with a high thermal neutron cross section such as 157Gd.     

Characterization of miniature tissue-equivalent proportional counters for neutron radiotherapy applications

A miniature tissue-equivalent proportional counter (TEPC) system has been developed to facilitate microdosimetric measurements in high-flux mixed fields. Counters with collecting volumes of 12.3 and 2.65 mm3 have been constructed using various tissue-equivalent wall materials, including those loaded with 10B for evaluation of the effects of the boron neutron capture reaction. These counters provide a measure of both the absorbed dose and associated radiation quality, allowing an assessment of the utility and relative effectiveness of various neutron radiotherapy techniques such as boron neutron capture therapy (BNCT), boron neutron capture enhanced fast neutron therapy (BNCEFNT) and intensity modulated neutron radiotherapy (IMNRT). An evaluation of the physical parameters affecting the measured microdosimetric spectrum, the gas multiplication characteristics and the measurement of absorbed dose is presented. In addition, important aspects of the calibration and low energy extrapolation techniques for the microdosimetric spectrum are provided.     

Boron neutron capture therapy for the treatment of cerebral gliomas. I. Theoretical evaluation of the efficacy of various neutron beams.

The technique of boron neutron capture therapy in the treatment of cerebral gliomas depends upon the selective loading of the tumor with a 10B-enriched compound and subsequent irradiation of the brain with low-energy neutrons. The charged particles produced in the 10B (n,alpha) 7Li reaction have ranges in tissue of less than 10 mum so that the dose distribution closely follows the 10B distribution even to the cellular level. The effectiveness of this therapy procedure is dependent not only on the 10B compound but on the spectral characteristics of the neutron source as well. Hence, an optimization of these characteristics will increase the chances of therapeutic success. Transport calculations using a neutral particle transport code have been made to determine the dose-depth distributions within a simple head phantom for five different incident neutron beams. Comparison of these beams to determine their relative therapeutic efficacy was made by the use of a maximum useable depth criterion. In particular, with presently available compounds, the MIT reactor (MITR) therapy beam (a) is not inferior to a pure thermal neutron beam, (b) would be marginally improved if its gamma-ray contamination were eliminated, (c) is superior to a partially 10B-filtered MITR beam, and (d) produces a maximum useable depth which is strongly dependent upon the tumor-to-blood ratio of 10B concentrations and weakly dependent upon the absolute 10B concentration in tumor. A pure epithermal neutron beam with a mean energy of 37 eV is shown to have close to the optimal characteristics for boron neutron capture therapy. Futhermore, these optimal characteristics can be approximated by a judiciously D2O moderated and 10B-filtered 252Cf neutron source. This tailored 252Cf source would have at least a 1.5 cm greater maximum useable depth than the MITR therapy beam for realistic 10B concentrations. However, at least one gram of 252Cf would be needed to make this a practical therapy source. If the moderated 252Cf source is not 10B filtered, the resultant neutron beam has characteristics similar to those of the MITR beam with no gamma-ray contamination. For usch a beam, 100 mg of 252Cf would produce a flux of 2.4 X 10(8) neutrons/(cm2 sec), which is an intensity suitable for therapy applications.     

On-line reconstruction of low boron concentrations by in vivo gamma-ray spectroscopy for BNCT

Boron neutron capture therapy (BNCT) is a radiation therapy in which the neutron capture reaction of 10B is used for the selective destruction of tumours. At the High Flux Reactor (HFR) in Petten, a therapy facility with an epithermal neutron beam has been built. In the first instance, patients with brain tumours will be treated. The doses delivered to the tumour and to the healthy tissue depend on the thermal neutron fluence and on the boron concentrations in these regions. An accurate determination of the patient dose during therapy requires knowledge of these time-dependent concentrations. For this reason, a gamma-ray telescope system, together with a reconstruction formalism, have been developed. By using a gamma-ray detector in a telescope configuration, boron neutron capture gamma-rays of 478 keV emitted by a small specific region can be detected. The reconstruction formalism can calculate absolute boron concentrations using the measured boron gamma-ray detection rates. Besides the boron gamma-rays, a large component of 2.2 MeV gamma-rays emitted at thermal neutron capture in hydrogen is measured. Since the hydrogen distribution is almost homogeneous within the head, this component can serve as a measure of the total number of thermal neutrons in the observed volume. By using the hydrogen gamma-ray detection rate for normalization of the boron concentration, the reconstruction tool eliminates the greater part of the influence of the inhomogeneity of the thermal neutron distribution. MCNP calculations are used as a tool for the optimization of the detector configuration. Experiments on a head phantom with 5 ppm 10B in healthy tissue showed that boron detection with a standard deviation of 3% requires a minimum measuring time of 2 min live time. From two position-dependent measurements, boron concentrations in two compartments (healthy tissue and tumour) can be determined. The reconstruction of the boron concentration in healthy tissue can be done with a standard deviation of 6%. The gamma-ray telescope can also be used for in vivo dosimetry.     

Dose distributions in a human head phantom for neutron capture therapy using moderated neutrons from the 2.5 meV proton-7Li reaction or from fission of 235U.

The feasibility of neutron capture therapy (NCT) using an accelerator-based neutron source of the 7Li(p,n) reaction produced by 2.5 MeV protons was investigated by comparing the neutron beam tailored by both the Hiroshima University radiological research accelerator (HIRRAC) and the heavy water neutron irradiation facility in the Kyoto University reactor (KUR-HWNIF) from the viewpoint of the contamination dose ratios of the fast neutrons and the gamma rays. These contamination ratios to the boron dose were estimated in a water phantom of 20 cm diameter and 20 cm length to simulate a human head, with experiments by the same techniques for NCT in KUR-HWNIF and/or the simulation calculations by the Monte Carlo N-particle transport code system version 4B (MCNP-4B). It was found that the 7Li(p,n) neutrons produced by 2.5 MeV protons combined with 20, 25 or 30 cm thick D20 moderators of 20 cm diameter could make irradiation fields for NCT with depth-dose characteristics similar to those from the epithermal neutron beam at the KUR-HWNIF.     

Validation of the scanning -gamma-ray telescope for in vivo dosimetry and boron measurements during BNCT.

Gamma-ray telescope scans of a box phantom with inhomogeneous boron concentrations have proven the feasibility of in vivo measurements of different boron distributions in the head of a patient during boron neutron capture therapy (BNCT). Small structures with enhanced boron concentration can be reconstructed in a head phantom, even if the brain compartment of the phantom is surrounded by a skin layer with a ten times higher boron concentration. The motor-controlled telescope can scan the head/phantom, detecting boron and hydrogen prompt y-rays emitted at neutron capture reactions with a two-dimensional spatial resolution of 14 mm full width at half maximum. For reconstruction of the boron concentrations from the measured y-ray detection rates, a mathematical reconstruction algorithm is derived and discussed. Proper reconstruction requires position-dependent y-ray measurements combined with treatment planning programme calculations of the thermal neutron distribution. In a head phantom, in which the brain and the skull (bulk) were represented using a homogeneous boron distribution of 5.2 +/- 0.5 ppm 10B, surrounded by a skin layer with a ten times higher boron concentration, the bulk concentration was reconstructed to 4.7 +/- 0.3 ppm 10B. Telescope scans along and perpendicular to the beam axis showed the influence of inhomogeneities with a high boron concentration such as skin and a simulated blood vessel, respectively with a low boron concentration such as white matter. The profiles of the boron and hydrogen y-ray detection rates indicate how future patient measurements can be interpreted. In clinical trials, the telescope can then be used to investigate the averaged boron concentration in the bulk of a patient and local enhanced boron concentrations (e.g. in tumour tissue) in order to relate the measured boron dose distributions to the clinical effects of BNCT. Simultaneously, it can serve as quality control of the dosimetry during the irradiation.     

Paired Mg and Mg(B) ionization chambers for the measurement of boron neutron capture dose in neutron beams

The use of the boron neutron capture (BNC) reaction to provide a dose enhancement in fast neutron therapy is currently under investigation at the Gershenson Radiation Oncology Center of Harper Hospital in Detroit, MI. The implementation of this treatment modality presents unique challenges in dosimetry. In addition to the measurement of photon and neutron doses in the mixed field, a measure of the thermal neutron flux and the associated boron neutron capture dose throughout the treatment volume is desired. A pair of small-volume magnesium ionization chambers has been constructed with the aim of providing this information. One of the chambers, denoted the Mg(B) chamber, is lined with a boron-loaded foil. The ionization response of this chamber has been calibrated in terms of BNC dose per ppm loading of 10B. These paired chambers can be used to map the local BNC response in neutron beams. From this data and an estimation of the boron concentration in the tumor and normal tissue, the boron neutron capture enhancement may be evaluated.     

Microanalytical techniques for boron analysis using the 10B(n,alpha)7Li reaction

In order to predict the efficacy of boronated compounds for neutron capture therapy (NCT), it is mandatory that the boron concentration in tissues be known. Various techniques for measurement of trace amounts of boron (1-100 ppm) are available, including chemical and physical procedures. Experience has shown that, with the polyhedral boranes and carboranes in particular, the usual colorimetric and spark emission spectroscopic methods are not reliable. Although these compounds may be traced with additional radiolabels, direct physical detection of boron by nondestructive methods is clearly preferable. Boron analysis via detection of the prompt-gamma ray from the 10B(n, alpha)7Li reaction has been shown to be a reliable technique. Two prompt-gamma facilities developed at Brookhaven National Laboratory are described. One, at the 60-MW high flux beam reactor, uses sophisticated beam extraction techniques to enhance thermal neutron intensity and reduce fast neutron and gamma contamination. The other was constructed at Brookhaven's 5-MW medical research reactor and uses conventional shielding and electronics to provide an "on-line" boron analysis facility adjacent to beams designed for NCT, thus satisfying one of the requisites for clinical application of this procedure. Technical restrictions attendant upon the synthesis and testing of boronated biomolecules often require the measurement of trace amounts of boron in extremely small (mg) samples. A track-etching technique capable of detecting ng amounts of boron in mg liquid or cell samples is described. Thus it is possible to measure the boron content in small amounts (mg samples) of antibodies, or boron uptake in cells grown in tissue culture.     

Boron neutron capture enhancement of fast neutron radiotherapy utilizing a moderated fast neutron beam

An investigation of the therapeutic potential of boron neutron capture (BNC) enhancement of fast neutron therapy utilizing the Harper University Hospital superconducting cyclotron-produced d(48.5)+Be fast neutron therapy beam is presented. A technique for modification of the fast neutron beam to increase the BNC enhancement is presented along with an evaluation of the effects of beam moderation on the biological effectiveness of the absorbed dose. Characteristics of the photon, neutron, and boron neutron capture components of the absorbed dose are presented. Results demonstrate the possibility of therapeutic gains greater than 50% over conventional fast neutron therapy at depths required to treat brain lesions. This enhancement is estimated assuming currently achievable boron concentrations, and is more than adequate to provide a therapeutic window for the effective treatment of Glioblastoma Multiforme without prohibitive toxicity to the normal brain.     

Performance characteristics of the MIT fission converter based epithermal neutron beam

A pre-clinical characterization of the first fission converter based epithermal neutron beam (FCB) designed for boron neutron capture therapy (BNCT) has been performed. Calculated design parameters describing the physical performance of the aluminium and Teflon filtered beam were confirmed from neutron fluence and absorbed dose rate measurements performed with activation foils and paired ionization chambers. The facility currently provides an epithermal neutron flux of 4.6 x 10(9) n cm(-2) s(-1) in-air at the patient position that makes it the most intense BNCT source in the world. This epithermal neutron flux is accompanied by very low specific photon and fast neutron absorbed doses of 3.5 +/- 0.5 and 1.4 +/- 0.2 x 10(-13) Gy cm2, respectively. A therapeutic dose rate of 1.7 RBE Gy min(-1) is achievable at the advantage depth of 97 mm when boronated phenylalanine (BPA) is used as the delivery agent, giving an average therapeutic ratio of 5.7. In clinical trials of normal tissue tolerance when using the FCB, the effective prescribed dose is due principally to neutron interactions with the nonselectively absorbed BPA present in brain. If an advanced compound is considered, the dose to brain would instead be predominately from the photon kerma induced by thermal neutron capture in hydrogen and advantage parameters of 0.88 Gy min(-1), 121 mm and 10.8 would be realized for the therapeutic dose rate, advantage depth and therapeutic ratio, respectively. This study confirms the success of a new approach to producing a high intensity, high purity epithermal neutron source that attains near optimal physical performance and which is well suited to exploit the next generation of boron delivery agents.     

Transport calculations of the influence of physical factors on depth-dose distributions in boron neutron capture therapy

Distributions of thermal neutron fluence and capture gamma ray absorbed dose rates were evaluated, taking into consideration various physical factors relevant to boron neutron capture therapy. The use of a larger neutron irradiation aperture was associated with an increase in thermal neutron fluence and capture gamma ray absorbed dose rates. Radiation leakage was more significant with smaller phantoms. Attenuation of thermal neutron fluence rates by 10B suggested that there was an optimal 10B concentration (less than 100 PPM) for a given tumour. Deuteration of water allowed better penetration of thermal neutrons with less capture gamma rays and is potentially applicable for the treatment of deep-seated brain tumours.     

Comparison of measured parameters from a 24-keV and a broad spectrum epithermal neutron beam for neutron capture therapy: an identification of consequential parameters

Epithermal neutron beams are under development in a number of locations in the U.S. and abroad. The increased penetration in tissue provided by these neurons should circumvent problems associated with the rapid attenuation of thermal neutron beams encountered in previous clinical trials of neutron capture therapy (NCT). Physical and radiobiological experiments with two "intermediate energy" or "epithermal" beams have been reported. A comparison is made here between the 24-keV iron-filtered beam at Harwell, England, and the broad-spectrum Al2 O3 moderated beam at the Brookhaven Medical Research Reactor (BMRR). In addition, parameters which are relevant for NCT, and which are best suited for evaluation and comparison of beams, are discussed. Particular attention is paid to the mean neutron energy which can be tolerated without significant reduction of therapeutic gain (TG), where TG is the ratio of tumor dose to maximum normal tissue dose. It is suggested that the simplest and most meaningful parameters for comparison of beam intensity and purity are the epithermal neutron fluence rate, and the fast neutron dose per epithermal neutron (4.2 X 10(-11) rad/neutron for the broad-spectrum beam and 29 X 10(-11) rad/neutron for the 24-keV beam). While the Al2O3 beam is close to optimal, the 24-keV beam produces a significant fast neutron dose which results in a lower TG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monte Carlo model of the Studsvik BNCT clinical beam: description and validation

The neutron beam at the Studsvik facility for boron neutron capture therapy (BNCT) and the validation of the related computational model developed for the MCNP-4B Monte Carlo code are presented. Several measurements performed at the epithermal neutron port used for clinical trials have been made in order to validate the Monte Carlo computational model. The good general agreement between the MCNP calculations and the experimental results has provided an adequate check of the calculation procedure. In particular, at the nominal reactor power of 1 MW, the calculated in-air epithermal neutron flux in the energy interval between 0.4 eV-10 keV is 3.24 x 10(9) n cm(-2) s(-1) (+/- 1.2% 1 std. dev.) while the measured value is 3.30 x 10(9) n cm(-20 s(-1) (+/- 5.0% 1 std. dev.). Furthermore, the calculated in-phantom thermal neutron flux, equal to 6.43 x 10(9) n cm(-2) s(-1) (+/- 1.0% 1 std. dev.), and the corresponding measured value of 6.33 X 10(9) n cm(-2) s(-1) (+/- 5.3% 1 std. dev.) agree within their respective uncertainties. The only statistically significant disagreement is a discrepancy of 39% between the MCNP calculations of the in-air photon kerma and the corresponding experimental value. Despite this, a quite acceptable overall in-phantom beam performance was obtained, with a maximum value of the therapeutic ratio (the ratio between the local tumor dose and the maximum healthy tissue dose) equal to 6.7. The described MCNP model of the Studsvik facility has been deemed adequate to evaluate further improvements in the beam design as well as to plan experimental work.     

Toward clinical application of prompt gamma spectroscopy for in vivo monitoring of boron uptake in boron neutron capture therapy

In boron neutron capture therapy (BNCT) the absorbed dose to the tumor cells and healthy tissues depends critically on the boron uptake. Pronounced individual variations in the uptake patterns have been observed for two boron compounds currently used in clinical trials. This implies a high uncertainty in the determination of the boron dose component. In the present work a technique known as prompt gamma spectroscopy (PGS) is studied that potentially can be used for in vivo and noninvasive boron concentration determination at the time of the treatment. The technique is based upon measurement of gamma rays promptly emitted in the 10B(n,alpha)7Li and 1H(n,gamma)2D reactions. The aim of this work is to prepare the present setup for clinical application as a monitor of boron uptake in BNCT patients. Therefore, a full calibration and a set of phantom experiments were performed in a clinical setting. Specifically, a nonuniform boron distribution was studied; a skin/ dura, a larger blood vessel, and tumor within a head phantom was simulated. The results show that it is possible to determine a homogeneous boron concentration of 5 microg/g within +/-3% (1 standard deviation). In the nonuniform case, this work shows that the boron concentration can be determined through a multistep measurement procedure, however, with a somewhat higher uncertainty (approximately 10%). The present work forms the basis for a subsequent clinical application of the PGS setup aimed at in vivo monitoring of boron uptake.     

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.     

Boron-loaded macromolecules in experimental physiology: tracing by neutron capture radiography

The search for suitable methods of attaching the boron isotope 10B to tumour cells in the human body for the treatment of malignant disease has prompted a study of ways of optimising the localisation of 10B in mammalian tissues. Compounds rich in boron, linked to various carriers, have been studied in experimental animals and in systems of cultivated cells. The current experimental prerequisites and results are outlined. The method for 'neutron capture radiography' has significant potential for general application in experimental physiology. The techniques are presented from this viewpoint and compared with other methods for visualisation of macromolecular markers by the use of physical or chemical principles.