Influence of the coating thickness and type of oral delivery system (tablets, pellets) on the stability towards degradation by neutron irradiation: Validation of neutron activation III

Enteric coated dexchlorpheniramine maleate (DCPA) tablets and pellets with varying coating thickness were subjected to several in vitro tests after irradiation by thermal neutrons in a flux of 1.1×10¹³ n cm⁻² s⁻¹ for 2, 4 or 15 min. The appearance of the tablet formulation changed extensively after exposure of the tablets to pile radiation. The irradiation caused the film to loosen from the surface of the core, indicating the generation of gases during the irradiation process. Already after irradiating the tablets for 2 min the disintegration and dissolution behaviour were significantly changed. The extent of tablet damage increased with increasing time of exposure and increasing thickness of the coating. Compared with the tablet formulation, the cores could resist a larger amount of irradiation since dissolution behaviour of the cores was only affected after 15 min of irradiation. This indicates that the irradiation procedure initially affects the coating of the formulation. Although the dissolution behaviour of the pellet formulations changed significantly after the irradiation procedure, the changes were too small to be attributed exclusively to radiation damage.     

Hyperthermia Enhances Thermal-Neutron–Induced Cell Death of Human Glioblastoma Cell Lines at Low Concentrations of B

Purpose: To examine the ability of pre- vs. post-irradiation hyperthermia to enhance the effectiveness of thermal neutrons to kill human glioblastoma cells.

Methods and Materials: Human glioblastoma cell lines, T98G, A7, A172, and U 87MG, were exposed to thermal neutrons from the Kyoto University Research (KUR) reactor or to ⁶⁰Co γ-rays. Hyperthermia was tested before and after irradiation of T98G (44°C, 15 min) and A7 cells (44°C, 40 min), and with different concentrations (0–30 ppm) of ¹⁰B-boric acid. The biological end point of all experiments was cell survival measured by a colony formation assay.

Results: The relative biological effectiveness (RBE) values of thermal neutrons for these cell lines compared with ⁶⁰Co γ-rays were 1.8–2.0 at their D₀ values. When T98G and A7 cells were heated after thermal neutron irradiation, there was a synergistic effect at low ¹⁰B concentrations (up to 5 ppm for T98G and up to 10 ppm for A7 cells). With high concentrations of boron (10–30 ppm for T98G and 20–30 ppm for A7 cells), hyperthermia and neutron irradiation interact additively rather than synergistically. There was no enhancement when cells were heated before thermal neutron irradiation. These results suggest that the radiosensitizing effect of hyperthermia may be attributed to partial inhibition of the repair of the potentially lethal damage caused by neutron irradiation.     

Gadolinium sheet converter for neutron radiography

This work describes a methodology developed for the confection of gadolinium sheet converter for neutron radiography using the gadolinium chloride (GdCl₃) as material converter. Though manufactured at a relatively low cost, they are as good as the sheet converter on the market. Here, we present neutron radiography of the penetrameter, the edge spread function, the modulation transfer function and characteristic curves for each set sheet-AA400 Kodak film.     

用体表24Naγ计数率评价事故中子照射注量与剂量的实验研究

目的研究用测量体表24Naγ初始计数率评价事故中子照射注量和剂量的新方法.方法实验用拟人模体进行.模体由头、颈、躯干、臀部和上臂构成.模体中具有按中国参考人大小的模拟器官脑、肝、肺、心脏和真骨.软组织用组织当量材料(液体)替代.组织当量材料中的氢、氮、氧、碳的质量比为10.6∶2.5∶63.2∶23.7,密度为1.007 g/cm3 (20 °C),肺的密度是0.3 g/cm3.一个252Cf中子源用于照射实验.中子对于模体的照射方向包括前面(AP)、后面(PA)、右侧(RLAT)及左侧(LLAT).252Cf中子源到模体的照射距离有1.1,2.1,3.1和4.1 m.在照射后用φ76 mm×76 mm的NaI和多道分析仪在模体体表的8个位置测量24Naγ.结果中子瞬时照射后,人体头顶部位的24Naγ在1.368 MeV到2.754 MeV能量区间每单位中子注量产生的初始计数率B随照射距离的增大而增大,但随照射方向的变化较小.如果模体内模拟器官和组织替代物中的钠含量与中国参考人一致,则可以推算出B的最大值Bm=0.48×10-7 cm2s-1.结论对于裂变中子照射, 在事故后利用头顶部位测量到的24Naγ初始计数率及Bm值可在几小时内估算出个人受照射的中子注量和剂量.按10 min的计数时间,该方法的灵敏度好于0.01 Gy总剂量.     

Application of spectral decomposition analysis to in vivo quantification of aluminum by neutron activation analysis

The toxic effects of aluminum are cumulative and result in painful forms of renal osteodystrophy, most notably adynamic bone disease and osteomalacia, but also other forms of disease. The Trace Element Group at McMaster University has developed an accelerator-based in vivo procedure for detecting aluminum body burden by neutron activation analysis (NAA). Further refining of the method was necessary for increasing its sensitivity. In this context, the present study proposes an improved algorithm for data analysis, based on spectral decomposition. A new minimum detectable limit (MDL) of (0.7±0.1) mg Al was reached for a local dose of (20±1) mSv. The study also addresses the feasibility of a new data acquisition technique, the electronic rejection of the coincident events detected by a NaI(Tl) system. It is expected that the application of this technique, together with spectral decomposition analysis, would provide an acceptable MDL for the method to be valuable in a clinical setting.     

D–D neutron generator development at LBNL

The plasma and ion source technology group in Lawrence Berkeley National Laboratory is developing advanced, next generation D–D neutron generators. There are three distinctive developments, which are discussed in this presentation, namely, multi-stage, accelerator-based axial neutron generator, high-output co-axial neutron generator and point source neutron generator. These generators employ RF-induction discharge to produce deuterium ions. The distinctive feature of RF-discharge is its capability to generate high atomic hydrogen species, high current densities and stable and long-life operation. The axial neutron generator is designed for applications that require fast pulsing together with medium to high D–D neutron output. The co-axial neutron generator is aimed for high neutron output with cw or pulsed operation, using either the D–D or D–T fusion reaction. The point source neutron generator is a new concept, utilizing a toroidal-shaped plasma generator. The beam is extracted from multiple apertures and focus to the target tube, which is located at the middle of the generator. This will generate a point source of D–D, T–T or D–T neutrons with high output flux. The latest development together with measured data will be discussed in this article.     

Classifying threats with a 14-MeV neutron interrogation system

SeaPODDS (Sea Portable Drug Detection System) is a non-intrusive tool for detecting concealed threats in hidden compartments of maritime vessels. This system consists of an electronic neutron generator, a gamma-ray detector, a data acquisition computer, and a laptop computer user-interface [Strellis et al., 2003, Proceedings of the 2003 ONDCP International Technology Symposium, San Diego, CA].

Although initially developed to detect narcotics, recent algorithm developments have shown that the system is capable of correctly classifying a threat into one of four distinct categories: narcotic, explosive, chemical weapon, or radiological dispersion device (RDD). Detection of narcotics, explosives, and chemical weapons is based on gamma-ray signatures unique to the chemical elements. Elements are identified by their characteristic prompt gamma-rays induced by fast and thermal neutrons. Detection of RDD is accomplished by detecting gamma-rays emitted by common radioisotopes and nuclear reactor fission products. The algorithm phenomenology for classifying threats into the proper categories is presented here.     

中子组织当量液的研制及其与水在模体实验中对24Na感生量的比较

目的研制可用于中子实验的液体组织当量材料，并检验其在拟人模体中子照射实验中测量24^Na活度浓度的适用性。方法根据ICRP23号出版物对人体软组织H、N、O、C四个元素的比例和密度要求，以及其他对实验的适用性要求，对18000余种化学物进行筛选、分析、计算和试验。结果研制了由下列材料和比例(％)组成的软组织替代物：水：乙醇：柠檬酸-水：N-甲基乙酰苯胺：甘氨酸：尿素=50．3：27．5：8．52：5．68：6．4：1．6。在该组织替代物中，四个元素的重量比(％)为H：N：O：C=10．6：2．5：63．2：23．7，密度为1．006～1．008g，crn3(20℃)。实验表明，当组织当量液被水替代时受252^Cf中子照射后模体内24^Na的活度浓度及长方体内活化的24^Na的分布都有较大差异。结论大量实际使用表明：该软组织替代物可方便地适用于人体模中子实验，并且不能用水替代。     

Accuracy and precision of absorbed dose measurements for neutron therapy

The occurrence of normal tissue complications and probability of tumor control are steep functions of absorbed dose. Consequently the delivery of the dose to the patient should be performed with a precision better than +/- 2% and an overall uncertainty less than +/- 5%. The sequence of dosimetry procedures to deliver the absorbed dose to the patient is analyzed with emphasis on the physical parameters involved in neutron dosimetry; the results of neutron dosimetry intercomparisons are summarized. The protocols for neutron dosimetry formulated by European and American physicists differ in a number of aspects, including the choice of the phantom material. For the treatment of a specific lesion, e.g., a tumor of the floor of the mouth, different treatment plannings have been suggested. Regarding the determination of total absorbed dose at a reference point in a phantom, the required overall uncertainty can be achieved for neutron energies up to 20 MeV. Because of differences in size, shape and composition between the phantom and the patient, somewhat larger uncertainties are to be anticipated for the actual treatment. Further experimental and theoretical studies are needed to obtain more reliable values for kerma in different elements and neutron sensitivity of the photon dosimeters for neutron energies in excess of 20 MeV.     

The european experience in neutron therapy at the end of 1981

We present here a survey of the European neutron therapy facilities. For head and neck tumors, the excellent results reported from Hammersmith were not confirmed by an EORTC combined trial (Amsterdam, Edinburgh and Essen). For salivary glands, high percentages (75%) of local control were obtained in Hammersmith and in Amsterdam, as well as in other centers. Following the promising results reported from Hammersmith, neutron therapy of soft tissue sarcomas was started in several centers. For patients with no clinical evidence of residual tumor after surgery, a local control rate ranging between 70% and 90% was achieved (Essen, Hamburg, Heidelberg, Louvain-la-Neuve). For patients with “gross” residual tumor, or with inoperable tumors, the percentages of local control vary within large limits (20–75% ) from center to center, probably according to differences in histology, tumor localization, tumor size or extention, and perhaps fractionation (Hammersmith, Edinburg, Amsterdam, Essen, Hamburg, Heidelberg, Louvain-la-Neuve). A study on bronchus carcinoma, performed in Heidelberg, did not show any benefit with neutron therapy. Patients with locally extended cervix and prostate carcinoma were treated in Louvain-la-Neuve according to the RTOG protocol; an excellent early tolerance was noticed. However, for both sites, it is too early to derive valid long term conclusions. For prostatic tumors, a complete regression is usually achieved. For bladder carcinoma, the results from Manchester did not indicate a significant difference between neutron and photon therapy, both in initial assessment of results and complications. The Amsterdam group came to similar conclusions.