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PubMed1996

Capillary optics for neutron capture therapy.

The development of capillary neutron optics permits a new technology for neutron capture therapy involving the application of a focused thermal neutron beam at the medically optimal location within the patient. A subthermal neutron beam begins to converge as it travels through a neutron "lens," reaching a narrow focus within a tube that allows it to pass directly to the treatment region. This technique results in a substantially lower dose to untreated parts of the patient and a substantially weaker radiation field in the treatment room generally. Additional advantages include the relative ease of thermal neutron generation and the ability to shield the patient completely and effectively from fast neutrons or gamma rays originating at the neutron source. This work describes the application of capillary optics to neutron capture therapy, along with Monte Carlo calculations of the neutron flux profiles within a patient for an optimized system design. Specific dose profiles for the case of boron neutron capture therapy within the brain are also provided.

Biophysical Phenomena↗

PubMedDate not supplied

Neutron capture therapy research in Australia.

Neutron capture therapy research in Australia has continued to grow since the first Australia-Japan workshop in April, 1986. The support base has broadened and the wide range of contributing laboratories includes universities, research institutes, and hospitals. Considerable progress has been made in boron chemistry--an accurate boron assay technique has been developed, boron analogues of chlorpromazine and thiouracil have been synthesised or nearly so, and decaborane conjugation with monoclonal antibodies has been achieved to the required loadings. In vitro cell survival experiments are proceeding in the Moata reactor using human melanoma and mouse cell lines incubated with enriched boronophenylalanine and boron tetraphenyl porphyrins. Electron microscopy examination of radiation damaged morphology shows considerable differences between cell lines. Progress with the nude mouse human melanoma model has been slow because of the lack of a reliable in vivo melanotic melanoma line, and the B16 mouse line is found to be more efficacious. Tailored beam calculations for the 10 MW HIFAR reactor indicate the difficulty of obtaining a suitable therapeutic beam because of the generated gamma dose in the beam filters. A new approach to NCT utilises the enormous cross section of 157Gd and the induced-Auger effect which has been shown to cause double strand breaks in circular DNA.

Animals↗

PubMed1989

The production by 72 MeV protons of keV neutrons for 10B neutron capture therapy.

Fast neutrons, produced in a spallation process by 72 MeV protons hitting heavy nuclei, can be moderated down to keV energies, suitable for 10B capture therapy. Measurements of neutron flux from copper and lead targets, after moderation by water and hydrocarbons, have been performed, together with measurements of the fast neutron and gamma-backgrounds. The comparisons with Monte Carlo calculations show good agreement. As neutron fluences up to 10(12) to 10(13)n/cm2 can be produced within a few hours in about 0.5 m target distance the technique seems to be suitable for clinical experiments.

Boron↗

PubMed1990

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.

Boron↗

PubMed2005

Approach to magnetic neutron capture therapy.

PURPOSE: The method of magnetic neutron capture therapy can be described as a combination of two methods: magnetic localization of drugs using magnetically targeted carriers and neutron capture therapy itself. METHODS AND MATERIALS: In this work, we produced and tested two types of particles for such therapy. Composite ultradispersed ferro-carbon (Fe-C) and iron-boron (Fe-B) particles were formed from vapors of respective materials. RESULTS: Two-component ultradispersed particles, containing Fe and C, were tested as magnetic adsorbent of L-boronophenylalanine and borax and were shown that borax sorption could be effective for creation of high concentration of boron atoms in the area of tumor. Kinetics of boron release into the physiologic solution demonstrate that ultradispersed Fe-B (10%) could be applied for an effective magnetic neutron capture therapy. CONCLUSION: Both types of the particles have high magnetization and magnetic homogeneity, allow to form stable magnetic suspensions, and have low toxicity.

Boron↗

PubMed1998

Biodistribution of p-boronophenylalanine in patients with glioblastoma multiforme for use in boron neutron capture therapy.

OBJECTIVE: The success of boron neutron capture therapy depends on the safety and specificity of the boron delivery agent. As a preface to clinical boron neutron capture therapy of glioblastoma multiforme, a biodistribution study of intravenous p-boronophenylalanine (BPA) in patients undergoing craniotomy for resection of glioblastoma was performed. METHODS: Varying doses of intravenously administered BPA-fructose (130-250 mg BPA per kilogram of body weight) were given to patients 2 to 3 hours prior to the start of craniotomy for either suspected or known glioblastoma multiforme. Blood samples were collected over a 48-hour period for boron assay. At surgery, multiple samples of tumor, brain, and scalp were obtained for boron and histological analysis. RESULTS: Seventeen patients were studied; all but one had glioblastoma multiforme. No adverse effects from the BPA infusions were noted. The boron concentration in the blood reached a maximum at the end of the BPA infusion and was proportional to the administered dose of BPA. Normal brain concentrations of boron generally were equal to or less than that in blood. Tumor-blood boron ratios were highly variable: 1.6 +/- 0.8 (mean +/- standard deviation; n = 187; range, 0.3-3.5). The observed heterogeneity of BPA uptake in glioblastoma samples appears to correlate with the degree of cellularity observed on histological examination. CONCLUSION: Intravenous BPA administration up to a dose of 250 mg/kg is safe and well tolerated. BPA uptake in surgical samples of glioblastoma tissue is variable and may depend on the fraction of viable tumor cells in the individual sample. Further clinical studies using BPA as a boron delivery agent for boron neutron capture therapy of glioblastoma multiforme appear warranted.

Boron Compounds↗

PubMed2002

Controllability of depth dose distribution for neutron capture therapy at the Heavy Water Neutron Irradiation Facility of Kyoto University Research Reactor.

The updating construction of the Heavy Water Neutron Irradiation Facility of the Kyoto University Research Reactor has been performed from November 1995 to March 1996 mainly for the improvement in neutron capture therapy. On the performance, the neutron irradiation modes with the variable energy spectra from almost pure thermal to epi-thermal neutrons became available by the control of the heavy-water thickness in the spectrum shifter and by the open-and-close of the cadmium and boral thermal neutron filters. The depth distributions of thermal, epi-thermal and fast neutron fluxes were measured by activation method using gold and indium, and the depth distributions of gamma-ray absorbed dose rate were measured using thermo-luminescent dosimeter of beryllium oxide for the several irradiation modes. From these measured data, the controllability of the depth dose distribution using the spectrum shifter and the thermal neutron filters was confirmed.

Antineoplastic Agents↗

PubMed2000

A Monte Carlo dosimetry-based evaluation of the 7Li(p,n)7Be reaction near threshold for accelerator boron neutron capture therapy.

Advanced methods of boron neutron capture therapy (BNCT) use an epithermal neutron beam in conjunction with tumor-targeting boron compounds for irradiation of glioblastomas and metastatic melanomas. A common neutron-producing reaction considered for accelerator-based BNCT is 7Li(p,n)7Be, whose cross section increases very rapidly within several tens of keV of the reaction threshold at 1.88 MeV. Operation in the proton energy region near threshold will have an appreciable thick target neutron yield, but the neutrons produced will have relatively low energies that require little moderation to reach the epithermal range desirable for BNCT. Because of its relatively low projected accelerator cost and the portability of the neutron source/target assembly, BNCT based on the near-threshold technique is considered an attractive candidate for widespread hospital use. A systematic Monte Carlo N-Particle (MCNP) investigation of the dosimetric properties of near-threshold neutron beams has been performed. Results of these studies indicate that accelerator proton energies between 1.93 and 1.99 MeV, using 5 cm of H2O moderator followed by thin 6Li and Pb shields, can provide therapeutically useful beams with treatment times less than one hour and accelerator currents less than 5 mA.

Beryllium↗

PubMed2001

Anaesthetic management of 27 cases of boron neutron capture therapy for glioblastoma.

Twenty-seven patients received boron neutron capture therapy during craniotomy at our research reactor from 1991 to 1999. This is a form of intra-operative radiation therapy, which uses neutrons from a nuclear reactor. There are three additional major problems to anaesthetists: boron neutron capture therapy must be given beside the nuclear reactor, with no hospital facilities; neutrons cannot be shielded effectively by ordinary protectors; and neutrons are detrimental to metal devices and especially to electrical appliances. Boron neutron capture therapy has been adopted as an effective therapy for glioblastoma/astrocytoma, but special considerations are required for anaesthesia.

Anesthesia, General↗

PubMedDate not supplied

Critical evaluation of bispecific antibodies as targeting agents for boron neutron capture therapy of brain tumors.

Boron neutron capture therapy (BNCT) is based on the nuclear capture reaction that occurs when 10B, a stable isotope, is irradiated with low energy neutrons to produce high linear energy transfer (LET) alpha particles and recoiling 7Li nuclei. In order for BNCT to be successful in treating cancer, approximately 10(9) boron atoms must be delivered per tumor cell to sustain a lethal 10B, (n,a) 7Li capture reaction. In the present study, we have produced and characterized a bispecific antibody (BsAbB8), which was reactive with both human glioma and melanoma cell lines, as well as with a variety of polyhedral borane anions (PBA). The affinity constants (KA) of BsAb-B8 with D-54 MG and M21 cells were 3.49 and 2.57 x 10(8) M-1, respectively, which were almost identical to those of the parental mAb 9.2.27 with these cell lines. In vivo tumor localizing properties were studied in nude mice bearing subcutaneous xenografts of the D-54 MG glioma. Following intravenous injection of 131I-labeled BsAb-B8, 3.4 +/- 0.2% of the injected dose/g was detected in the tumor at 24 hours, and then slowly declined to 2.0 +/- 0.4% at 96 hours compared to 1.34 +/- 0.07% and 0.03 +/- 0.01%, respectively, for normal mouse IgG. Based on the assumption that all the tumor cell antigenic receptor sites could be saturated, the following calculations have been carried out. The maximum concentration of BsAb-B8 that could be delivered to 1 g of D-54 MG glioma cells would be 99.6 micrograms, which could bind 71.7 ng of a PBA. However, since at least 500 x more boron would be required per gram of tumor to sustain a lethal 10B (n,a) 7Li capture reaction, a macromolecule containing -10(3)-10(4) boron atoms rather than a low molecular weight PBA would be required to deliver this amount. Such boron containing macromolecules have been synthesized by us, and future studies should provide information on the feasibility of using them in combination with BsAb-B8 to deliver the requisite amount of 10B.

Animals↗

PubMed2000

Boron neutron capture therapy for malignant gliomas.

Boron neutron capture therapy (BNCT) represents a promising modality for a relatively selective radiation dose delivery to the tumour tissue. Boron-10 nuclei capture slow 'thermal' neutrons preferentially and, upon capture, promptly undergo 10B(n,alpha)7Li reaction. The ionization tracks of energetic and heavy lithium and helium ions resulting from this reaction are only about one cell diameter in length (approximately 14 microm). Because of their high linear energy transfer (LET) these ions have a high relative biological effectiveness (RBE) for controlling tumour growth. The key to effective BNCT of tumours, such as glioblastoma multiforme (GBM), is the preferential accumulation of boron-10 in the tumour, including the infiltrating GBM cells, as compared with that in the vital structures of the normal brain. Provided that a sufficiently high tumour boron-10 concentration (approximately 10(9) boron-10 atoms/cell) and an adequate thermal neutron fluence (approximately 10(12) neutrons/cm2) are achieved, it is the ratio of the boron-10 concentration in tumour cells to that in the normal brain cells that will largely determine the therapeutic gain of BNCT.

Boron Neutron Capture Therapy↗

PubMed2006

Design of a rotating facility for extracorporal treatment of an explanted liver with disseminated metastases by boron neutron capture therapy with an epithermal neutron beam.

In 2001, at the TRIGA reactor of the University of Pavia (Italy), a patient suffering from diffuse liver metastases from an adenocarcinoma of the sigmoid was successfully treated by boron neutron capture therapy (BNCT). The procedure involved boron infusion prior to hepatectomy, irradiation of the explanted liver at the thermal column of the reactor, and subsequent reimplantation. A complete response was observed. This encouraging outcome stimulated the Essen/Petten BNCT group to investigate whether such an extracorporal irradiation could be performed at the BNCT irradiation facility at the HFR Petten (The Netherlands), which has very different irradiation characteristics than the Pavia facility. A computational study has been carried out. A rotating PMMA container with a liver, surrounded by PMMA and graphite, is simulated using the Monte Carlo code MCNP. Due to the rotation and neutron moderation of the PMMA container, the initial epithermal neutron beam provides a nearly homogeneous thermal neutron field in the liver. The main conditions for treatment as reported from the Pavia experiment, i.e. a thermal neutron fluence of 4 x 10(12) +/- 20% cm(-2), can be closely met at the HFR in an acceptable time, which, depending on the defined conditions, is between 140 and 180 min.

Computer Simulation↗

PubMed2002

Calculation of dose components in head phantom for boron neutron capture therapy.

Application of neutrons to cancer treatment has been a subject of considerable clinical and research interest since the discovery of the neutron by Chadwick in 1932 (3). Boron neutron capture therapy (BNCT) is a technique of radiation oncology which is used in treating brain cancer (glioblastoma multiform) or melanoma and that consists of preferentially loading a compound containing 10B into the tumor location, followed by the irradiation of the patient with a beam of neutron. Dose distribution for BNCT is mainly based on Monte Carlo simulations. In this work, the absorbed dose spatial distribution resultant from an idealized neutron beam incident upon ahead phantom is investigated using the Monte Carlo N-particles code, MCNP 4B. The phantom model used is based on the geometry of a circular cylinder on which sits an elliptical cylinder capped by half an ellipsoid representing the neck and head, both filled with tissue-equivalent material. The neutron flux and the contribution of individual absorbed dose components, as a function of depths and of radial distance from the beam axis (dose profiles) in phantom model, is presented and discussed. For the studied beam the maximum thermal neutron flux is at a depth of 2 cm and the maximum gamma dose at a depth of 4 cm.

Boron Neutron Capture Therapy↗

PubMed1997

Strategic planning workshop on research needs for neutron capture therapy.

The workshop 'Research Needs for Neutron Capture Therapy', held in Williamsburg, VA, May 9-12. 1995 addressed key issues and questions related to optimization of boron neutron capture therapy (BNCT), in general, and to the possibility of success of the present BNCT trials at the Brookhaven National Laboratory (BNL) and Massachusetts Institute of Technology (MIT), in particular. Both trials use nuclear fission reactors as neutron sources for BNCT of glioblastoma multiforme (BNL) and of deep seated melanoma (MIT). Presentations and discussions focussed on optimal boron-labeled compounds, mainly for brain tumors such as glioblastoma multiforme, and the best mode of compound delivery to the tumor. Also, optimizing neutron irradiation with dose delivery to the tumor cells and the issues of dosimetry of BNCT especially in the brain were discussed. Planning of treatment and of follow-up of patients, coordination of BNCT at various treatment sites, and the potential of delivery BNCT to various types of cancer with an appropriately tailored protocol were additional issues. The need for multicentric interdisciplinary cooperation among the different medical specialties was highlighted.

Boron Neutron Capture Therapy↗

PubMedDate not supplied

Synthesis and in vitro evaluation of the phenylboric acid derivative entrapped lipiodol in boron neutron capture therapy for hepatoma.

BACKGROUND: Hepatoma, a common cancer in Taiwan, responds poorly to conventional therapies. Boron neutron capture therapy (BNCT) may provide a promising approach for hepatoma therapy. In this study, a pharmaceutical composition, phenylboric acid derivative entrapped lipiodol (PBAD-lipiodol), was synthesized and characterized. In vitro study was used for evaluation of PBAD-lipiodol for the BNCT of hepatoma. MATERIALS AND METHODS: alpha Track observation was used to identify the boron compound in the TLC plate and to evidence the uniform distribution of boron in the PBAD-lipiodol. Inductively coupled plasma-atomic emission spectroscopy and neutron activation analysis were used to determine the concentrations of boron and lipiodol, respectively. Human hepatoma HepG2 cells were used for in vitro experiments. A Nomarski optical microscope was used to investigate the uptake of PBAD-lipiodol globules in individual hepatoma cells. RESULTS: PBAD-lipiodol was stable in human serum. The boron source, PBAD, was uniformly distributed in PBAD-lipiodol. Many of the PBAD-lipiodol globules were internalized and retained in HepG2 cells, and the boron concentration of HepG2 cells reached 269 ppm after 72 hours of PBAD-lipiodol treatment. CONCLUSION: In vitro studies revealed that PBAD-lipiodol could deliver a therapeutically effective amount of PBAD as a boron source for the BNCT of hepatoma. PBAD-lipiodol is a potential new boron drug for the BNCT of hepatoma.

Boron Neutron Capture Therapy↗

PubMedDate not supplied

A prototype epithermal neutron beam for boron neutron capture therapy.

An epithermal neutron beam has been designed and tested at the Georgia Institute of Technology's 5-MW Research Reactor. The prototype facility consists of aluminum and sulfur disks in a tangential beam port for fast neutron filtration. A cadmium sheet at the port exit removes the thermal neutrons from the transmitted beam, leaving an intensely epithermal neutron beam spanning five energy decades, each contributing to the flux demanded by boron neutron capture therapy. The thermal neutron flux generated by the incident epithermal neutrons in a polyethylene head phantom peaks at a depth of 3 cm and remains above the incident thermal flux to a 7-cm depth. The beam thus provides the penetration required for treating deep-seated gliomas. Photon contamination in the prototype facility is high, and a number of basic modifications are proposed for reducing it to safer levels.

Boron↗

PubMed1992

Microdosimetry for boron neutron capture therapy.

Preclinical studies for boron neutron capture therapy (BNCT) using epithermal neutrons are ongoing at several laboratories. The absorbed dose in tumor cells is a function of the thermal neutron flux at depth, the microscopic boron concentration, and the size of the cell. Dosimetry is therefore complicated by the admixture of thermal, epithermal, and fast neutrons, plus gamma rays, and the array of secondary high-linear-energy-transfer particles produced within the patient from neutron interactions. Microdosimetry can be a viable technique for determining absorbed dose and radiation quality. A 2.5-cm-diameter tissue-equivalent gas proportional counter has been built with 50 parts per million (ppm) 10B incorporated into the walls and counting gas to simulate the boron uptake anticipated in tumors. Measurements of lineal energy (y) spectra for BNCT in simulated volumes of 1-10 microns diameter show a dose enhancement factor of 4.3 for 30 ppm boron, and a "y" of 250 keV/microns for the boron capture process. Chamber design plus details of experimental and calculated linear energy spectra will be presented.

Boron↗

PubMed1995

Bispecific antibodies as targeting agents for boron neutron capture therapy of brain tumors.

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10, a stable isotope, is irradiated with low energy (< or = 0.025 eV) or thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. A major requirement for the success of BNCT is the selective delivery of a sufficient number of boron atoms (approximately 10(9)) to individual cancer cells to sustain a lethal 10B (n, alpha) 7Li capture reaction. A panel of BsAb reactive with polyhedral borane anions (PBA) and a tumor-associated chondroitin sulfate proteoglycan has been produced. All of these BsAb showed strong reactivity with a panel of human glioblastoma and melanoma cell lines, as demonstrated by indirect membrane immunofluorescence. Two of them (H6 and B8) also reacted with cells that had been exposed to PBA (Na2B10H10 and Na2B12H11SH) and a boronated starburst dendrimer, which contained approximately 250-400 B atoms per molecule. The affinity constant (Ka) of BsAb-B8 was 2.57 x 10(8) M-1 on M21 human melanoma cell and 3.49 x 10(8) M-1 on A172 glioblastoma cells, which were almost identical to those of the parental monoclonal antibody (mAb) 9.2.27 on the same cell lines (2.62 x 10(8) M-1). Since our BsAb recognize both human glioblastoma and melanoma-associated antigens, as well as PBA, they potentially could be used to target 10B to these tumors for BNCT.

Animals↗