Radiation spectra for Auger-electron emitting radionuclides: report No. 2 of AAPM Nuclear Medicine Task Group No. 6.

Radiation spectra for radionuclides currently provided by the MIRD Committee and ICRP do not include the very low-energy N- and O-shell Auger electrons. These electrons, emitted in large numbers by radionuclides decaying by electron capture and/or internal conversion, are important for determining the absorbed dose in microscopic volumes. Accordingly, the present AAPM Report employs Monte Carlo computational methods to obtain a self-consistent set of complete radiation spectra for a variety of radionuclides including 55Fe, 67Ga, 99mTc, 111In, 113mIn, 115mIn, 123I, 125I, 193mPt, 195mPt, 201Tl, and 203Pb. Although the conventional spectra provided by MIRD and ICRP are adequate for most dosimetry calculations, the Auger electron spectra provided in this report are recommended for calculating the dose to target volumes < 1 microns in diameter.     

用于硼中子俘获治疗的加速器超热中子源靶的设计

提出适合硼中子俘获治疗加速器^7Li(p,n)^7Be反应中子源一 个金属锂靶的设计，并对中子产额进行了计算。用MonteCarlo的方法研究了中子在水中的慢化和反射层对中子能谱的影响。结果表明，在这种几何结构下^7Li(p,n)^7Be反应产生的中子经过5cm的水层慢化后可作为硼中子俘获治疗的超热中子源。     

Irradiation characteristics of BNCT using near-threshold 7Li(p,n)7Be direct neutrons: application to intra-operative BNCT for malignant brain tumours

A calculation method for the dosage of neutrons by near-threshold 7Li(p, n)7Be and gamma rays by 7Li(p, p'gamma)7Li was validated through experiments with variable distance between the Li target and the phantom, focusing on large angular dependence. The production of neutrons and gamma rays in the Li target was calculated by Lee's method and their transport in the phantom was calculated using the MCNP-4B code. The dosage in intra-operative boron neutron capture therapy (BNCT) using near-threshold 7Li(p, n)7Be direct neutrons was evaluated using the validated calculation method. The effectiveness of the usage of the direct neutrons was confirmed from the existence of the region satisfying the requirements of the protocol utilized in intra-operative BNCT for brain tumours in Japan. The boron-dose enhancer (BDE) introduced in this paper to increase the contribution of the 10B(n, alpha)7Li dose in the living body was effective. The void utilized to increase the dose in deep regions was also effective with BDE. For the investigation of 1.900 MeV proton beams, for example, it was found that intraoperative BNCT using near-threshold 7Li(p, n)7Be direct neutrons is feasible.     

Enhancement of neutron radiation dose by the addition of sulphur-33 atoms

The use of neutrons in radiotherapy allows the possibility of producing nuclear reactions in a specific target inserted in the medium. (10)B is being used to induce reactions (n, alpha), a technique called boron neutron capture therapy. I have studied the possibility of inducing a similar reaction using the nucleus of (33)S, for which the reaction cross section presents resonances for keV neutrons, the highest peak occurring at 13.5 keV. Here shown, by means of Monte Carlo simulation of point-like sources of neutrons in this energy range, is an enhancement effect on the absorbed dose in water by the addition of (33)S atoms. In addition to this, as the range of the alpha particle is of the order of a mammalian cell size, the energy deposition via this reaction results mainly inside the cells adjacent to the interaction site. The main conclusion of the present work is that the insertion of these sulphur atoms in tumoral cells would enhance the effect of neutron irradiation in the keV range.     

Physical and chemical limitations to preparation of beta radioactive stents by direct neutron activation

Pure beta emitters are the sources of choice for intracoronary irradiations in restenosis prevention. In this work we reconsidered preparation of low activity 32P sources by ion-implantation of stable 31P into highly biocompatible pure titanium stents, followed by neutron activation. Gamma-spectrometrical analysis has shown that during activations with high thermal neutrons flux production of gamma-active long-lived contaminants is much beyond the dosimetrically acceptable limit, mainly due to the competing (n,p) reactions induced by the fast neutrons on isotopes of the bulk stent material, and to a lesser extent due to (n,gamma) reactions on chemical impurities. A potential applicability of this method for obtaining alternative beta radioactive stents is discussed.     

Measurement of total body nitrogen and oxygen by irradiation with cyclotron neutrons and 'delayed' gamma ray counting

Measurement of total body nitrogen is assuming increasing importance in the nutritional evaluation of seriously ill patients. Nitrogen has been previously measured either by counting (i) the annihilation radiation from 13N immediately after neutron irradiation with 14 MeV neutrons or (ii) the 'prompt' gamma rays from thermal neutron capture by 14N during irradiation with 14 MeV neutrons or with those produced by isotopic sources or a cyclotron. The present work describes studies into the feasibility of measuring 13N produced by irradiation with a neutron beam from the MRC Cyclotron. A complication of this method is that 13N is also produced in a reaction with 16O. Direct measurement of oxygen by use of the reactions 16O(n, p)16N or 16O(n, 2n)15O enables this interference to be estimated. The former reaction is possible with both 14 meV and cyclotron-produced neutrons but the 7.1 s half-life of 16N requires detectors to be placed in or very close to the irradiation site. In our particular circumstances this is not possible but the more energetic cyclotron neutron spectrum allows the production of 15O which has a half-life of 2.05 min and can be measured in a remote whole-body counter. A disadvantage with the cyclotron beam, in comparison with 14 MeV neutrons, is that a higher dose is required for similar accuracy. A reproducibility of about 4% is obtained with a dose equivalent of 0.01 Sv.     

16O(n, p)16N: a fast neutron detector for rapid tissue inhomogeneity correction

We have devised a transit dose technique for fast neutron therapy treatment planning based on the 16O(n, p)16N reaction in recirculating water, and have determined the effect of simulated bone and lung inhomogeneities in phantom. An effective threshold of 10.2 MeV in the 16O(n, p) reaction is exploited to detect transmitted neutrons without the need detector collimation. This system has been demonstrated with 14 MeV (d, T) neutrons and with cyclotron produced p(42) + Be neutrons. 16N decays to the 6.13 MeV excited states of 16O in 7.14 s, allowing for easy identification by NaI(T1) and for rapid recirculation. The transmission of fast neutrons can thus be related to an effective thickness of soft tissue, providing a rapid and direct measure of the effects of inhomogeneities under actual treatment conditions, with the 10 MeV threshold providing a useful degree of insensitivity to multiply scattered neutrons. Equivalent thickness of compact bone and lung relative to water were found to be 1.4 and 0.34 respectively, closely resembling the effective thicknesses for Cobalt-60 gamma rays.     

Unifying dose specification between clinical BNCT centers in the Americas

A dosimetry intercomparison between the boron neutron capture therapy groups of the Massachusetts Institute of Technology (MIT) and the Comisión Nacional de Energía Atómica (CNEA), Argentina was performed to enable combined analyses of NCT patient data between the different centers. In-air and dose versus depth measurements in a rectangular water phantom were performed at the hyperthermal neutron beam facility of the RA-6 reactor, Bariloche. Calculated dose profiles from the CNEA treatment planning system NCTPlan that were calibrated against in-house measurements required normalizations of 1.0 (thermal neutrons), 1.13 (photons), and 0.74 (fast neutrons) to match the dosimetry of MIT.     

Radioprotective effects of amifostine (WR-2721) or cystamine on radiation damage and its repair in rats whole body exposed to fission neutrons

Sulphur containing radioprotective drugs amifostine (gammaphos, WR-2721) or cystamine (disulfide of meracaptoethylamine) of Czechoslovak production were examined in whole body fission neutrons irradiated rats in the thermal column of reactor VVR-S. Using the split-dose technic the first sublethal neutron dose in the range 1-2 Gy was followed by second lethal exposures in the two time intervals (3 or 6 days) using whole body fission neutrons irradiations (3 days interval) or whole body gamma-irradiations (6 days interval) for LD50/30 evaluation within next 30 days survival observation. In other experiments the mean survival time (MST) in days was estimated in different rats group, when animals were whole body fission neutrons irradiated twice with 3-days interval using the total lethal doses of 4 or 5 Gy. Protected rats received amifostine (160 mg.kg(-1) i.p. and 200 mg.kg(-1) i.m.) or cystamine (40 mg.kg(-1) i.p. and 50 mg.kg(-1) i.m.), control rats obtained saline 20 min before beginning of irradiation in the amount of 0.5 ml.100 g(-1) of the rat's body weight. Non-significant DRF value 1.13 for WR-2721 i.p. was calculated in survival studies in rats twice neutron irradiated with 3 days interval (DRF 1.04 for cystamine). Chemical protectors were administered before each neutron exposure. MST of twice neutron lethal iradiated rats was prolonged not regularly by radioprotectors tested. WR-2721 and cystamine i.m. were not able to increase 6 days reparation processes after sublethal 2 Gy fission neutrons whole body irradiated rats.     

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.     

Time course of the inflammatory response to histamine and allergen skin prick test in guinea-pigs.

Plasma exudation and vasodilatation are key microvascular features of acute inflammation. Exudation and vasodilatation responses in the weal area after skin prick testing with histamine are essentially completed within 30 min. There is evidence to suggest that vasodilatation lasts considerably longer after provocation with allergen, but there is no information on the duration of plasma exudation. The purpose of this study was to measure the time course of the microvascular inflammatory response in the skin after histamine and allergen provocation. Skin prick tests were performed with histamine, allergen (ovalbumin) or saline (control) on guinea-pigs which were shaved on their backs. Radioactive 113mIn was used to label transferrin as a plasma tracer. Radioactivity was recorded from the superficial part of the skin by external detection of conversion electrons from the decay of 113mIn. The increase in count rate, corresponding to tracer accumulation by vasodilatation and/or plasma exudation, was used as a measure of the microvascular inflammatory response to skin prick test. The microvascular response was studied immediately and up to 30 min after provocation. The largest response to histamine and allergen occurred immediately after provocation. The exudative response then gradually declined to be absent after 25-30 min. Skin prick test with saline resulted in a small response of shorter duration. We conclude that the microvascular reaction to histamine as well as allergen provocation in guinea-pig skin has a rapid onset and a duration of approximately 30 min.     

Irritation effects of residual products derived from poly(2-hydroxyethyl methacrylate) gels. I. Testing of some model compounds

2-Hydroxyethyl methacrylate (HEMA) monomer and sodium benzoate, diluted with saline in the range 0-20%, were tested for intradermal irritation in rats. Radioactive indicator (113mIn) was used to quantify this biological response. At low concentrations (up to 1%) only a little irritation was recorded, while at higher levels (5% or more) a significant adverse reaction developed. The degree of irritation was dose dependent. In the concentration range 0-10%, the response was exponential. Model decomposition products derived from three different polymerization initiators were also tested. How the results obtained with the model irritants relate to real polymerization systems is discussed.     

Significantly improved accuracy of diagnosis of early Lyme disease by peptide enzyme-linked immunosorbent assay based on the borreliacidal antibody epitope of Borrelia burgdorferi OspC

Highly specific borreliacidal antibodies are induced by infection with Borrelia burgdorferi, and the immunodominant response during early Lyme disease is specific for an epitope within the 7 amino acids nearest the C terminus of OspC. We evaluated the ability of an enzyme-linked immunosorbent assay (ELISA) based on a synthetic peptide (OspC7) that matched the region to detect the response and compared the sensitivity during early Lyme disease to that for an FDA-approved Western blot. When the optical density value was adjusted to 98% specificity based on the results from testing normal or uncharacterized sera (n = 236) or sera from patients with blood factors or illnesses that commonly produce antibodies that cross-react with B. burgdorferi antigens (n = 77), 115 (73%) of 157 sera from patients likely to have early Lyme disease were positive for immunoglobulin M (IgM) antibodies and 17 (11%) also had IgG antibodies. In addition, the IgM ELISA reactivities and the titers of antibodies detected by a flow cytometric borreliacidal antibody test correlated closely (r = 0.646). Moreover, the IgM ELISA was significantly more sensitive (P < 0.001) than the Western blot procedure. The findings therefore confirmed that the peptide IgM ELISA detected OspC borreliacidal antibodies and provided strong evidence that the test can eliminate the necessity for confirming early Lyme disease by a supplementary test such as Western blotting.     

Light scattering study of irradiated lipid bilayer.

Vesicular phospholipid bilayer membranes in the form of giant unilamellar vesicles (GUVs) of dipalmitoylphosphatidylcholine (DPPC) were irradiated with fast neutron fluences ranging from 10(4) to 10(7) n cm-2. The phase behaviour of both non-irradiated and irradiated GUVs was investigated using an angular light scattering technique. A model independent size distribution of the samples and their optical anisotropy (delta) were determined using a maximum entropy technique and the theory of light scattering from spherical shells composed of anisotropic cylindrical molecules arranged radially in the shells. The structural changes in the lipid bilayer exposed to fission neutrons are discussed on the basis of the damaging mechanisms of fast neutrons to both the hydrophobic and hydrophilic regions of the lipid bilayer.     

Immunolocalization of Le(y) oligosaccharide in endometrium during menstrual cycle and effect of early luteal phase mifepristone administration on its expression in implantation stage endometrium of the rhesus monkey

Changes in carbohydrate expression on endometrial and blastocyst cell surfaces may play a critical role in the process of implantation. Le(y) is an oligosaccharide antigen which has been shown to be involved in blastocyst attachment in the mouse. In the present study, immunohistochemical distribution of Le(y) in endometrium during proliferative and secretory phases of normal menstrual cycles in the rhesus monkey was examined. Endometrial samples were collected on cycle days 7 (n=4), 13 (n= 4), 16 (n=4), 20 (n=4) and 25 (n=3). There was a gradual increase of Le(y) in luminal surface from proliferative to periovulatory (P < 0.001), and from periovulatory to postovulatory (P < 0.05), phases. Le(y) then remained constant in the midsecretory phase and decreased (P < 0.01) during the premenstrual phase. Le(y) score in glands did not change between the phases, except in midsecretory phase when it was higher than that in other phases (P < 0.05). The stromal compartment showed no statistically significant changes. The profiles of endometrial Le(y) on day 6 after ovulation in mated fecund cycles with or without early luteal phase mifepristone treatment were also examined. Females were allowed to cohabit with males during days 8-16 of their ovulatory cycles and were injected s.c. with vehicle (n=7) only, or with a single dose of mifepristone (2 mg/kg body weight; n=8) on day 2 after ovulation. Significant decreases in the area and optical absorption of immunoprecipitate were observed in the epithelial compartment (P < 0.01) following mifepristone treatment. There was no change in the stromal compartment either in area or in optical absorption of immunoprecipitate for Le(y) with or without mifepristone treatment. The expression of Le(y) in the endometrial epithelial compartment appears to be influenced by progesterone and may be associated with endometrial receptivity prior to implantation in the rhesus monkey.      

Measurements of low-energy (d,n) reactions for BNCT. Boron Neutron Capture Therapy.

Neutron yields and energy spectra have been measured for various deuteron-induced reactions at low energy. Neutrons of energy > 100 keV emitted in the 9Be(d,n)10B, 12C(d,n)13N, and 13C(d,n)14N reactions at Ed= 1.5 MeV were detected at five angles by means of liquid scintillator detectors. While low-energy neutrons were observed in all studied reactions, only 13C(d,n)14N is characterized by a relatively large yield with spectral features potentially interesting for an accelerator-based neutron source for BNCT.     

Fast neutron yields and spectra from targets of varying atomic number bombarded with deuterons from 16 to 50 MeV.

Neutron production from targets of Be, C, Mo, Cu, Ta and Au bombarded with deuterons of 16, 33 and 50 MeV has been studied at the isochronous cyclotron at Louvain-la-Neuve. Neutron spectra were measured by the time of flight method. The yields of neutrons and gamma rays were also measured, and the greatest ratio of neutrons to gamma rays in the forward direction was found to occur with 50 MeV deuterons on a Be target. The angular distribution of neutrons from Be was measured at 16, 33 and 50 MeV, and neutron spectra were measured as function of angle with 50 MeV deuterons on Be.     

Improvement of ESR dosimetry for thermal neutron beams through the addition of gadolinium

In this paper, the addition of gadolinium is proposed as a useful tool to enhance the electron spin resonance (ESR) sensitivity of organic compounds to thermal neutrons. The target of this work is the detection, through the ESR technique, of the thermal neutron fluence in a mixed field of photons and neutrons. Gadolinium was chosen because it has a very high capture cross section to thermal neutrons; its nuclear reaction with thermal neutrons induces complex inner shell transitions that generate, besides other particles, Auger electrons, which in turn release their energy in the neighborhood (only several nanometers) of the place of reaction. Gadolinium was added to two organic molecules: alanine and ammonium tartrate. The main result obtained was a greater neutron sensitivity for dosimeters with gadolinium than for those without gadolinium for both organic molecules used. Since a dosimeter pair is required to discriminate between the two components of a mixed field, we studied the response of each dosimeter pair irradiated in a mixed field. Through a blind test we verified the usefulness of this dosimetric system and we obtained an estimate of the fluence in the mixed field with a relative uncertainty of 3%, when the pair composed of an alanine dosimeter and a dosimeter with alanine and gadolinium is used.     

Assessment of organ-specific neutron equivalent doses in proton therapy using computational whole-body age-dependent voxel phantoms

Proton beams used for radiotherapy will produce neutrons when interacting with matter. The purpose of this study was to quantify the equivalent dose to tissue due to secondary neutrons in pediatric and adult patients treated by proton therapy for brain lesions. Assessment of the equivalent dose to organs away from the target requires whole-body geometrical information. Furthermore, because the patient geometry depends on age at exposure, age-dependent representations are also needed. We implemented age-dependent phantoms into our proton Monte Carlo dose calculation environment. We considered eight typical radiation fields, two of which had been previously used to treat pediatric patients. The other six fields were additionally considered to allow a systematic study of equivalent doses as a function of field parameters. For all phantoms and all fields, we simulated organ-specific equivalent neutron doses and analyzed for each organ (1) the equivalent dose due to neutrons as a function of distance to the target; (2) the equivalent dose due to neutrons as a function of patient age; (3) the equivalent dose due to neutrons as a function of field parameters; and (4) the ratio of contributions to secondary dose from the treatment head versus the contribution from the patient's body tissues. This work reports organ-specific equivalent neutron doses for up to 48 organs in a patient. We demonstrate quantitatively how organ equivalent doses for adult and pediatric patients vary as a function of patient's age, organ and field parameters. Neutron doses increase with increasing range and modulation width but decrease with field size (as defined by the aperture). We analyzed the ratio of neutron dose contributions from the patient and from the treatment head, and found that neutron-equivalent doses fall off rapidly as a function of distance from the target, in agreement with experimental data. It appears that for the fields used in this study, the neutron dose lateral to the field is smaller than the reported scattered photon doses in a typical intensity-modulated photon treatment. Most importantly, our study shows that neutron doses to specific organs depend considerably on the patient's age and body stature. The younger the patient, the higher the dose deposited due to neutrons. Given the fact that the risk also increases with decreasing patient age, this factor needs to be taken into account when treating pediatric patients of very young ages and/or of small body size. The neutron dose from a course of proton therapy treatment (assuming 70 Gy in 30 fractions) could potentially (depending on patient's age, organ, treatment site and area of CT scan) be equivalent to up to approximately 30 CT scans.     

Reliability of the transcutaneous PO2 measurement in the adult by the TCM 1 radiometer electrode

The accuracy of transcutaneous PO2 measurements (PtcO2; Radiometer TCM 1) was evaluated by comparison with arterial PO2 (PaO2) on 115 recordings in 35 patients: 20 during exercise testing (group I) and 14 during assisted ventilation at different FIO2 values (group II). The correlation coefficient between PaO2 and PtcO2 was satisfactory (r = 0.977; n = 115). However PaO2 and PtcO2 mean values were significantly different in group I, and in group II at 45% FIO2. The analysis of variance showed that the difference between PaO2 and PtcO2 was significant among the patients but did not vary with exercise and FIO2 changes (group I: F19 = 6.28, p less than 0.001; group II: F19(19) = 2.54, p less than 0.025). In the adult, transcutaneous PO2 measurement by TCM 1 radiometer electrode seems to be interesting in the context of monitoring blood gases with exercise and assisted ventilation. The significant variation with arterial PO2 sometimes registered should make one cautious in the interpretation of accurate measurements.