Robert M. Brugger

Boron neutron capture therapy of brain tumors: past history, current status, and future potential.

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. High-grade astrocytomas, glioblastoma multiforme, and metastatic brain tumors constitute a major group of neoplasms for which there is no effective treatment. There is growing interest in using BNCT in combination with surgery to treat patients with primary, and possibly metastatic brain tumors. For BNCT to be successful, a large number of 10B atoms must be localized on or preferably within neoplastic cells, and a sufficient number of thermal neutrons must reach and be absorbed by the 10B atoms to sustain a lethal 10B(n, alpha)7 Li reaction. Two major questions will be addressed in this review. First, how can a large number of 10B atoms be delivered selectively to cancer cells? Second, how can a high fluence of neutrons be delivered to the tumor? Two boron compounds currently are being used clinically, sodium borocaptate (BSH) and boronophenylalanine (BPA), and a number of new delivery agents are under investigation, including boronated porphyrins, nucleosides, amino acids, polyamines, monoclonal and bispecific antibodies, liposomes, and epidermal growth factor. These will be discussed, and potential problems associated with their use as boron delivery agents will be considered. Nuclear reactors, currently, are the only source of neutrons for BNCT, and the fission process within the core produces a mixture of lower-energy thermal and epithermal neutrons, fast or high (> 10,000 eV) energy neutrons, and gamma rays. Although thermal neutron beams have been used clinically in Japan to treat patients with brain tumors and cutaneous melanomas, epithermal neutron beams should be more useful because of their superior tissue-penetrating properties. Beam sources and characteristics will be discussed in the context of current and future BNCT trials. Finally, the past and present clinical trials on BNCT for brain tumors will be reviewed and the future potential of BNCT will be assessed.

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.

The prompt gamma neutron activation analysis facility at Murr

Abstract A facility has been developed at the University of Missouri Research Reactor so that the unique features of prompt gamma-ray neutron activation analysis can be used to measure trace and major elements in samples. This facility consists of a radial beamport, external sample position with shielding, and a multi-mode counting system. A single-crystal silicon neutron filter installed inside the beamport passes most of the thermal neutrons while reducing fast neutron and gamma radiation associated with the beam. Using thin gold foils, the beam was measured at the sample position to be 5 × 108n cm−2 s−1, with a cadmium ratio of 42 1 . Background measurements of thermal and fast neutrons at the Ge(Li) detector yielded 1 and 2 n cm−2 s−1, respectively. The multimode counting system consists of a Ge(Li) detector surrounded by an annular NaI crystal both of which are controlled by a computer-based analyzer system. Prompt gamma-ray spectra were collected in the energy range from 0.05 to 11 MeV. To establish the performance capabilities of the facility, irradiations of pure element or simple compound standards were performed to identify the prompt gamma-ray energies from each element, their count rates, and their interferences. Preliminary results are presented demonstrating the application of this technique to the analysis of standard reference materials.

Double-difference method to improve the resolution of an eV neutron spectrometer

Abstract Epithermal (eV) neutron spectrometers designed to measure the dynamic properties of condensed matter have been developed at several pulsed neutron sources, using nuclear resonances to define neutron energy. The energy resolution of such a spectrometer is limited by the width of the nuclear resonance. The paper describes how a linear combination of measurements with two thicknesses of foils of the resonance material yields better energy resolution than either foil alone. With proper selection of foil thicknesses, there is no penalty in counting statistics to obtain the improved resolution. The double-difference method also suppresses the wings of the resonance and yields a function with a finite second moment so that uncertainties may be properly propagated.

A single crystal silicon thermal neutron filter

Abstract Single crystals of silicon have been examined as thermal neutron filters and found to be quite effective. While the free atom cross section is 2.25 b, the cross section near thermal was measured to be σ (54meV, 300 K)=0.54b and σ (54meV, 77 K )=0.25 b.

Neutron computed tomography

Abstract: 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.

A versatile neutron beam filter facility with silicon and iron filters

Abstract A versatile neutron beam filter facility has been installed at the University of Missouri Research Reactor Facility (MURR). With this facility, the filter tubes can be changed easily and safely during a reactor shutdown while the components within a filter tube can be inserted or removed with the reactor operating at low power. To date two filters have been made for this facility. The Si filter provides a 144 keV neutron flux of about 106 n/cm2s, and the Fe filter a 24 keV neutron flux of about 107 n/cm2 s. Spectrum measurements through 210 cm of single crystal Si have shown that an increase in the thickness of Si significantly reduces the intensity of both the gamma and low energy neutron background.

Thermal neutron driven, 14.1 MeV neutron generators

Abstract A detailed theoretical and experimental study of the production of 14.1 MeV neutrons from thermal neutrons using simple convertors has been performed. These convertors rely on the absorption of a thermal neutron resulting in a triton which interacts with deuterium producing a 14.1 MeV neutron. Three different systems have been studied: 6 LiD, 6 LiOD D 2 O and 3 He D 2 . In general the agreement between theory and experiment is good demonstrated efficiencies of approximately 2×10 −4 are observed. Based upon these results, theoretical optimization studies have been performed and possible applications have been discussed.

Low Energy Accelerator-Based Neutron Sources for Neutron Capture Therapy

Neutron beams for neutron capture therapy (NCT) have been studied by a number of investigators,1,2,3 using high flux research reactors as the source of neutrons. There are very few research reactors in the world, probably less than ten, that can meet the conditions of both flux intensity and neutron energy spectrum. Hence the availability of NCT for patients with malignant brain tumors would be quite limited, even if all of these reactors would be able to accommodate the necessary beam design and hospital room atmosphere into the operational program.

Additional experimental tests of the Bonner sphere neutron spectrometer

Abstract In a continued effort to experimentally test Bonner sphere spectrometer systems, the results reported in this paper include: (1) a new partial illumination correction factor which has been determined to correct an error in the previous work, (2) a new spectral unfolding code, BONABS, which has been included in these tests (in addition to the previously used SWIFT code) and (3) scandium and uranium filtered beams which have been measured. The results indicate a small improvement in energy prediction capabilities due to the corrected partial illumination factor and reasonable agreement between the SWIFT and BONABS unfolding codes for the spectra tested.