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Biomedical subjects

R M Brugger

Publications and source records attributed to R M Brugger.

13 recordsLinked to original sources

Physical and biological doses produced from neutron capture in a 235U foil.

As a follow-on study to the feasibility of neutron capture therapy (NCT) with 235U brachytherapy seeds, physical doses were calculated and measured for the radiation from a 235U foil in a lucite phantom which was irradiated at the epithermal neutron irradiation port of the Brookhaven Medical Research Reactor. In addition, cell survival experiments were performed to obtain the relative biological effectiveness (RBE) for the neutron part of the radiation. The calculated absorbed doses agree with the measured ones. From cell survival experiments, it is deduced that the fission neutrons from the 235U foil have a RBE of 3.0 while the fast neutrons in the beam have a RBE of 3.8. Also observed is that, with the cells 7 mm from the foil, a significant amount of absorbed dose comes from the beta rays of 235U fission events. This absorbed dose from beta rays is a significant addition to the therapeutic dose. Due to the limited ranges of beta rays in tissue, this absorbed dose is restricted to the vicinity of the foil. This is the first demonstration of beta rays as part of NCT.

Beta Particles

Enhancement of the epithermal neutron beam used for boron neutron capture therapy.

PURPOSE: This report describes a study to enhance the epithermal neutron beam at the Brookhaven Medical Research Reactor by increasing the epithermal neutron flux and/or reducing contamination by fast neutrons. METHODS AND MATERIALS: The beam was reevaluated using Monte Carlo calculations and flux and dose measurements in air and in an ellipsoidal head phantom at the patient irradiation port. Changes in its geometry and materials were considered, including rearranging the fuel elements in the reactor core and redesigning the moderator and the patient irradiation port. RESULTS: Calculations of the new fluxes and doses at the patient irradiation port showed that the epithermal neutron flux can be increased by 100%, while the fast neutron dose per epithermal neutron can be reduced by 38%. In 1992, some of the proposed changes were made. In June 1992, measurements were made after one additional fuel element was added to replace a graphite spacer block on the epithermal beam side of the reactor core. The results show that the epithermal neutron flux increased by 18%, as predicted by the Monte Carlo calculations. In October 1992, the fuel elements in the reactor core were rearranged by placing four new fuel elements in the first row facing the epithermal port; the intensity of the epithermal neutron beam increased by 50% and the fast neutron and gamma doses per epithermal neutron may have decreased slightly. CONCLUSION: The epithermal neutron beam at the Brookhaven Medical Research Reactor has gained a 50% increase in the epithermal neutron flux and the fast neutron and gamma doses per epithermal neutron are reduced slightly after the rearrangement of the fuel elements in the core.

Boron Neutron Capture Therapy

Design of a high-flux epithermal neutron beam using 235U fission plates at the Brookhaven Medical Research Reactor.

Beams of epithermal neutrons are being used in the development of boron neutron capture therapy for cancer. This report describes a design study in which 235U fission plates and moderators are used to produce an epithermal neutron beam with higher intensity and better quality than the beam currently in use at the Brookhaven Medical Research Reactor (BMRR). Monte Carlo calculations are used to predict the neutron and gamma fluxes and absorbed doses produced by the proposed design. Neutron flux measurements at the present epithermal treatment facility (ETF) were made to verify and compare with the computed results where feasible. The calculations indicate that an epithermal neutron beam produced by a fission-plate converter could have an epithermal neutron intensity of 1.2 x 10(10) n/cm2.s and a fast neutron dose per epithermal neutron of 2.8 x 10(-11) cGy.cm2/nepi plus being forward directed. This beam would be built into the beam shutter of the ETF at the BMRR. The feasibility of remodeling the facility is discussed.

Boron Neutron Capture Therapy

Boron neutron capture therapy for cancer. Realities and prospects.

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10 (10B), is irradiated with low-energy thermal neutrons (nth) to yield (4He) alpha-particles and 7Li nuclei (10B+nth-->[11B]-->4He+7Li+2.31 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of 10B and nth to individual cancer cells to sustain a lethal 10B(n, alpha) 7Li reaction. The current review covered the radiobiologic considerations on which BNCT is based, including a brief discussion of microdosimetry and normal tissue tolerance. The development of tumor-localizing boron compounds was discussed, including the sulfhydryl-containing polyhedral borane, sodium borocaptate (Na2B12H11SH), and boronophenylalanine (BPA), both of which are currently being used clinically in Japan as capture agents for malignant brain tumors and melanomas, respectively. Compounds currently under evaluation, such as boronated porphyrins, nucleosides, liposomes, and monoclonal antibodies (MoAbs), were also considered. Nuclear reactors have been used as the exclusive source of neutrons for BNCT. The use of low-energy (0.025 eV) thermal neutrons and higher-energy (1-10,000 eV) epithermal beams, beam optimization, and possible alternative neutron sources (accelerators) were also discussed. Clinical studies performed in the United States during the 1950s and 1960s for the treatment of malignant brain tumors were reviewed. Current studies in Japan and future studies in Europe and the United States concerning the treatment of glioblastomas and melanomas by BNCT were discussed, as were critical issues that must be addressed if BNCT is ever to be a useful therapeutic modality.

Boron Neutron Capture Therapy

Intermediate energy neutron beams from the MURR.

Several reactors in the United States are potential candidates to deliver beams of intermediate energy neutrons for NCT. At this time, moderators, as compared to filters, appear to be the more effective means of tailoring the flux of these reactors. The objective is to sufficiently reduce the flux of fast neutrons while producing enough intermediate energy neutrons for treatments. At the University of Missouri Research Reactor (MURR), the code MCNP has recently been used to calculate doses in a phantom. First, "ideal" beams of 1, 35, and 1000 eV neutrons were analyzed to determine doses and advantage depths in the phantom. Second, a high quality beam that had been designed to fit in the thermal column of the MURR, was reanalyzed. MCNP calculations of the dose in phantom in this beam confirmed previous calculations and showed that this beam would be a nearly ideal one with neutrons of the desired energy and also a high neutron current. However, installation of this beam will require a significant modification of the thermal column of the MURR. Therefore, a second beam that is less difficult to build and install, but of lower neutron current, has been designed to fit in MURR port F. This beam is designed using inexpensive A1, S, and Pb. The doses calculated in the phantom placed in this beam show that it will be satisfactory for sample tests, animal tests, and possible initial patient trials. Producing this beam will require only modest modifications of the existing tube.

Facility Design and Construction

Neutron computed tomography.

A neutron-transmission computed tomography scanning system has been built for scanning biological materials. An oxygen filtered beam of 2.35 MeV neutrons was used for the measurements. The studies to date show that the interactions of these energy neutrons with samples simulating biological materials are more sensitive than X-rays to variations in the content of the material, thus providing the ability to produce high quality images. The neutron scans suggest that neutrons can be an effective radiation for the imaging of biological materials.

Mathematics

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

Neutron capture therapy with 235U seeds.

A combination of brachytherapy and neutron capture therapy has been evaluated using 235U metal seeds and external neutron beam irradiation. When thermal neutrons are absorbed by 235U, high-energy neutrons and gamma rays are produced and some of these deposit energy in surrounding tissue. A Monte Carlo program, using the code MCNP, has been used to evaluate two sizes of 235U seeds in a water phantom. The results of flux suppression around the seeds and dose distributions are illustrated and discussed. The results show that high doses can be delivered in a relatively short time by using 235U seeds with neutron capture therapy. This therapy with multiple needles or seeds can be envisioned as a substitute for traditional brachytherapy to give an effective killing dose.

Brachytherapy

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.

Animals

Neutron induced brachytherapy: a combination of neutron capture therapy and brachytherapy.

Brachytherapy is a widely used radiation therapy modality while neutron capture therapy is being intensely studied. These methods provide some advantages, but also have limitations that might be ameliorated by combining them. A technique that uses stable solid seeds or needles of Gd which are irradiated in vivo with neutrons has been evaluated. Monte Carlo calculations show that 5000 cGy of prompt gamma dose can be delivered to a treatment volume of 40 cm3 with a three-plane implant of 9-Gd needles. The tumor to normal tissue advantage of this method is as good as brachytherapy using 60Co seeds. Measurements of prompt gamma dose with films and TLD-700s in a lucite phantom verify the Monte Carlo evaluation. Dose measurements of a Gd needle in air also show that Gd is promising for this form of brachytherapy.

Brachytherapy