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A New Simplified System for the Evaluation of BNCT Pharmaceuticals

Description: A system for testing potential BNCT pharmaceuticals in cell cultures has been developed with the cooperation of Oak Ridge National Laboratory (ORNL), the University of Tennessee Chemistry Department and the University of Tennessee Nuclear Engineering Department. A BNCT test model has been established with the use of the human lung cancer cell line A 549. These cells were maintained in standard laboratory facilities and subjected to boronated chemicals. Following toxicity studies the human luug cancer cells were exposed to {sup 252}Cf neutron sources provided by the Radiochemical Engineering Development Center (REDC) at ORNL The isotope {sup 252}Cf performs effectively for BNCT applications. The neutron spectrum is similar to that of a reactor fission source with an average energy of 2.1 MeV. A 50 mg source of {sup 252}Cf moderated by water provides a source on the order of 1 x 10{sup 9} thermal neutrons/cm{sup 2}/sec at a distance of 3 cm. The half-life of {sup 252}Cf is 2.65 years, and thus may provide a simple and reliable source of neutrons for BNCT in locations without suitable nuclear reactors. The REDC of ORNL stores and processes the U.S. stockpile of {sup 252}Cf.
Date: September 13, 1998
Creator: Byrne, T.E.; Kabalka, G.W.; Martin, R.C. & Miller, L.F.
Partner: UNT Libraries Government Documents Department

Medical Applications of Gadolinium and/or Boron-Labeled Pharmaceuticals

Description: Boron neutron capture therapy (BNCT) is a binary treatment modality that can selectively irradiate tumor tissue. The key to effective BNCT is the preferential accumulation of <sup>10</sup>B in the tumor relative to the surrounding normal tissues. A screening procedure was developed under this CRADA that is an improvement over previously reported techniques. This method was used to evaluate the two compounds produced by BBI, the amino acid p-boronophenylalanine (BPA)and the sulfhydryl boroane N<sub>2</sub>B<sub>12</sub>H<sub>11</sub>SH (BSH), for clinically useful accumulation in a panel of human tumor cell lines. BPA showed selective accumulation in: squamous cell carcinoma of the lung; small cell carcinoma of the lung; osteosarcoma; prostate carcinoma; and ovarian carcinoma. Of these it was decided to pursue application of BPA-based BNCT to lung tumors. BPA distribution in nude mice bearing subcutaneous human lung tumor xenografts showed very favorable results. At 3 hours post-injection, the tumor/blood boron concentration ratio was 5:1, the tumorflung ratio was 6:1. The treatment planning sofiware, already in use for the glioblastoma BNCT clinical trial underway at BNL, was used for simulation of a human lung tumor treatment using BNCT. Input data for this simulation included the nude mouse biodistribution data, human lung tumor CT geometry, and the same assumptions about relative biological effectiveness of the BNCT dose components currently in use for the human brain tumor trial. The results of this lung tumor simulation indicate significant sparing of normal lung compared to tumor. We conclude that the BBI product BPA has potential applications in BNCT of other tumor sites. BPA-based BNCT for human small cell carcinoma of the lung looks promising. Further studies into the radiation biology of the normal lung will be required prior to clinical BNCT for lung tumors.
Date: October 1, 1997
Creator: Coderre, J A & Spielvogel, B
Partner: UNT Libraries Government Documents Department

Clinical trials of boron neutron capture therapy [in humans] [at Beth Israel Deaconess Medical Center][at Brookhaven National Laboratory]

Description: Assessment of research records of Boron Neutron Capture Therapy was conducted at Brookhaven National Laboratory and Beth Israel Deaconess Medical Center using the Code of Federal Regulations, FDA Regulations and Good Clinical Practice Guidelines. Clinical data were collected from subjects' research charts, and differences in conduct of studies at both centers were examined. Records maintained at Brookhaven National Laboratory were not in compliance with regulatory standards. Beth Israel's records followed federal regulations. Deficiencies discovered at both sites are discussed in the reports.
Date: May 29, 2001
Creator: Wallace, Christine
Partner: UNT Libraries Government Documents Department

Subcellular boron and fluorine distributions with SIMS ion microscopy in BNCT and cancer research

Description: The development of a secondary ion mass spectrometry (SIMS) based technique of Ion Microscopy in boron neutron capture therapy (BNCT) was the main goal of this project, so that one can study the subcellular location of boron-10 atoms and their partitioning between the normal and cancerous tissue. This information is fundamental for the screening of boronated drugs appropriate for neutron capture therapy of cancer. Our studies at Cornell concentrated mainly on studies of glioblastoma multiforme (GBM). The early years of the grant were dedicated to the development of cryogenic methods and correlative microscopic approaches so that a reliable subcellular analysis of boron-10 atoms can be made with SIMS. In later years SIMS was applied to animal models and human tissues of GBM for studying the efficacy of potential boronated agents in BNCT. Under this grant the SIMS program at Cornell attained a new level of excellence and collaborative SIMS studies were published with leading BNCT researchers in the U.S.
Date: May 30, 2008
Creator: Chandra, Subhash
Partner: UNT Libraries Government Documents Department

A Small-Animal Irradiation Facility for Neutron Capture Therapy Research at the RA-3 Research Reactor

Description: The National Atomic Energy Commission of Argentina (CNEA) has constructed a thermal neutron source for use in Boron Neutron Capture Therapy (BNCT) applications at the RA-3 research reactor facility located in Buenos Aires. The Idaho National Laboratory (INL) and CNEA have jointly conducted some initial neutronic characterization measurements for one particular configuration of this source. The RA-3 reactor (Figure 1) is an open pool type reactor, with 20% enriched uranium plate-type fuel and light water coolant. A graphite thermal column is situated on one side of the reactor as shown. A tunnel penetrating the graphite structure enables the insertion of samples while the reactor is in normal operation. Samples up to 14 cm height and 15 cm width are accommodated.
Date: November 1, 2007
Creator: Pozzi, Emiliano; Nigg, David W.; Miller, Marcelo; Thorp, Silvia I.; Schwint, Amanda E.; Heber, Elisa M. et al.
Partner: UNT Libraries Government Documents Department

An Accelerator Neutron Source for BNCT

Description: The overall goal of this project was to develop an accelerator-based neutron source (ABNS) for Boron Neutron Capture Therapy (BNCT). Specifically, our goals were to design, and confirm by measurement, a target assembly and a moderator assembly that would fulfill the design requirements of the ABNS. These design requirements were 1) that the neutron field quality be as good as the neutron field quality for the reactor-based neutron sources for BNCT, 2) that the patient treatment time be reasonable, 3) that the proton current required to treat patients in reasonable times be technologially achievable at reasonable cost with good reliability, and accelerator space requirements which can be met in a hospital, and finally 4) that the treatment be safe for the patients.
Date: March 14, 2006
Creator: Blue, Thomas, E
Partner: UNT Libraries Government Documents Department

Ninth international symposium on radiopharmacology

Description: The goal of this Symposium is to provide a forum for those international scientists involved in applying the principles of pharmacology and radiation biology to the development of agents for the diagnosis and treatment of disease. The program will highlight state-of-the-art progress in the development of those agents used in conjunction with some form of radiation such as radiopharmaceuticals, radiopaques, photo- and radiosensitizing drugs, and neutron capture agents. An underlying pharmacokinetic parameter associated with all these agents is the need for site-specific delivery to an organ or tumor. Therefore, a major goal of the symposium will be to address those pharmacologic principles for targeting molecules to specific tissue sites. Accordingly, session themes will include receptor-mediated processes, membrane transporters, antibody interactions, metabolic trapping, and oligonucleotide-antisense mechanisms.
Date: December 31, 1995
Partner: UNT Libraries Government Documents Department

Comparisons of TORT and MCNP dose calculations for BNCT treatment planning

Description: The relative merit of using a deterministic code to calculate dose distributions for BNCT applications were examined. The TORT discrete deterministic ordinated code was used in comparison to MCNP4A to calculate dose distributions for BNCT applications
Date: December 31, 1996
Creator: Ingersol, D.T.; Slater, C.O.; Williams, L.R.; Redmond, E.L., II & Zamenhof, R.G.
Partner: UNT Libraries Government Documents Department

An in-phantom comparison of neutron fields for BNCT

Description: Previously, the authors have developed the in-phantom neutron field assessment parameters T and D (Tumor) for the evaluation of epithermal neutron fields for use in BNCT. These parameters are based on an energy-spectrum-dependent neutron normal-tissue RBE and the treatment planning methodology of Gahbauer and his co-workers, which includes the effects of dose fractionation. In this paper, these neutron field assessment parameters were applied to The Ohio State University (OSU) design of an Accelerator Based Neutron Source (ABNS) (hereafter called the OSU-ABNS) and the Brookhaven Medical Research Reactor (BMRR) epithermal neutron beam (hereafter called the BMRR-ENB), in order to judge the suitability of the OSU-ABNS for BNCT. The BMRR-ENB was chosen as the basis for comparison because it is presently being used in human clinical trials of BNCT and because it is the standard to which other neutron beams are most often compared.
Date: January 1, 1998
Creator: Woollard, J.E.; Blue, T.E. & Capala, J.
Partner: UNT Libraries Government Documents Department

Final Report: 8th International Symposium on NCT for Cancer, May 15, 1998 - May 15, 1999

Description: The 8th International Symposium on Neutron Capture Therapy for Cancer (8th ISNCTC) was held in La Jolla, CA on Sept. 13-18, 1998. This biennial meeting of the International Society for Neutron Capture Therapy (ISNCT) was hosted by Society President M.F. Hawthorne (UCLA Dept. of Chemistry and Biochemistry). The Symposium brought together scientists (300 registrants from 21 countries) from diverse fields to report the latest developments in NCT. Topics of the 275 papers presented (30 plenary lectures, 81 oral presentations, and 164 posters) included the physics of neutron sources, chemistry of tumor-targeting agents, dosimetry, radiobiological studies, and clinical applications.
Date: September 1, 1999
Creator: Hawthorne, M.F.
Partner: UNT Libraries Government Documents Department

Carborane derivative development for boron neutron capture therapy. Final report

Description: Boron Neutron Capture Therapy [BNCT] is a binary method of cancer therapy based on the capture of neutrons by a boron-10 atom [{sup 10}B]. Cytotoxic {sup 7}Li nuclei and {alpha}-particles are emitted, with a range in tissue of 9 and 5 {micro}m, respectively, about one cell diameter. The major obstacle to clinically viable BNCT is the selective localization of 5-30 ppm {sup 10}B in tumor cells required for effective therapy. A promising approach to BNCT is based on hydrophilic boron-rich oligomeric phosphate diesters, or ''trailers'' that have been shown to concentrate selectively in tumor tissue. Examples of these compounds were prepared previously at high cost using an automated DNA synthesizer. Direct synthesis methods are needed for the production of gram-scale quantities for further biological evaluation. The work accomplished as a result of the collaboration between Fluorochem, Inc. and UCLA demonstrates that short oligomers containing at least five carborane units with four phosphodiester linkages can be prepared in substantial quantities. This work was accomplished by the application of standard phosphoramidite coupling chemistry.
Date: April 1, 1999
Creator: Barnum, Beverly A.; Hao, Yan; Moore, Roger; Hawthorne, M. Frederick & Baum, Kurt
Partner: UNT Libraries Government Documents Department

Microdosimetric investigations at the fast neutron therapy facility at Fermilab

Description: Microdosimetry was used to investigate three issues at the neutron therapy facility (NTF) at Fermilab. Firstly, the conversion factor from absorbed dose in A-150 tissue equivalent plastic to absorbed dose in ICRU tissue was determined. For this, the effective neutron kerma factor ratios, i.e., oxygen tissue equivalent plastic and carbon to A-150 tissue equivalent plastic, were measured in the neutron beam. An A-150 tissue equivalent plastic to ICRU tissue absorbed dose conversion factor of 0.92 {+-} 0.04 was determined. Secondly, variations in the radiobiological effectiveness (RBE) in the beam were mapped by determining variations in two related quantities, e{sup *} and R, with field size and depth in tissue. Maximal variation in e{sup *} and R of 9% and 15% respectively were determined. Lastly, the feasibility of utilizing the boron neutron capture reaction on boron-10 to selectively enhance the tumor dose in the NTF beam was investigated.
Date: December 1, 1997
Creator: Langen, K.M.
Partner: UNT Libraries Government Documents Department

Microdosimetry for Boron Neutron Capture Therapy

Description: The specific aims of the research proposal were as follows: (1) To design and construct small volume tissue equivalent proportional counters for the dosimetry and microdosimetry of high intensity thermal and epithermal neutron beams used in BNCT, and of modified fast neutron beams designed for boron neutron capture enhanced fast neutron therapy (BNCEFNT). (2) To develop analytical methods for estimating the biological effectiveness of the absorbed dose in BNCT and BNCEFNT based on the measured microdosimetric spectra. (3) To develop an analytical framework for comparing the biological effectiveness of different epithermal neutron beams used in BNCT and BNCEFNT, based on correlated sets of measured microdosimetric spectra and radiobiological data. Specific aims (1) and (2) were achieved in their entirety and are comprehensively documented in Jay Burmeister's Ph.D. dissertation entitled ''Specification of physical and biologically effective absorbed dose in radiation therapies utilizing the boron neutron capture reaction'' (Wayne State University, 1999). Specific aim (3) proved difficult to accomplish because of a lack of sufficient radiobiological data.
Date: September 5, 2000
Creator: Maughan, R.L. & Kota, C.
Partner: UNT Libraries Government Documents Department

Optimal Neutron Source & Beam Shaping Assembly for Boron Neutron Capture Therapy

Description: There were three objectives to this project: (1) The development of the 2-D Swan code for the optimization of the nuclear design of facilities for medical applications of radiation, radiation shields, blankets of accelerator-driven systems, fusion facilities, etc. (2) Identification of the maximum beam quality that can be obtained for Boron Neutron Capture Therapy (BNCT) from different reactor-, and accelerator-based neutron sources. The optimal beam-shaping assembly (BSA) design for each neutron source was also to e obtained. (3) Feasibility assessment of a new neutron source for NCT and other medical and industrial applications. This source consists of a state-of-the-art proton or deuteron accelerator driving and inherently safe, proliferation resistant, small subcritical fission assembly.
Date: April 30, 2003
Creator: Vujic, J.; Greenspan, E.; Kastenber, W.E.; Karni, Y.; Regev, D.; J.M. Verbeke, K.N. Leung et al.
Partner: UNT Libraries Government Documents Department

The therapeutic ratio in BNCT: Assessment using the Rat 9L gliosarcoma brain tumor and spinal cord models

Description: During any radiation therapy, the therapeutic tumor dose is limited by the tolerance of the surrounding normal tissue within the treatment volume. The short ranges of the products of the {sup 10}B(n,{alpha}){sup 7}Li reaction produced during boron neutron capture therapy (BNCT) present an opportunity to increase the therapeutic ratio (tumor dose/normal tissue dose) to levels unprecedented in photon radiotherapy. The mixed radiation field produced during BNCT comprises radiations with different linear energy transfer (LET) and different relative biological effectiveness (RBE). The short ranges of the two high-LET products of the `B(n,a)`Li reaction make the microdistribution of the boron relative to target cell nuclei of particular importance. Due to the tissue specific distribution of different boron compounds, the term RBE is inappropriate in defining the biological effectiveness of the {sup 10}B(n,{alpha}){sup 7}Li reaction. To distinguish these differences from true RBEs we have used the term {open_quotes}compound biological effectiveness{close_quotes} (CBE) factor. The latter can be defined as the product of the true, geometry-independent, RBE for these particles times a {open_quotes}boron localization factor{close_quotes}, which will most likely be different for each particular boron compound. To express the total BNCT dose in a common unit, and to compare BNCT doses with the effects of conventional photon irradiation, multiplicative factors (RBEs and CBEs) are applied to the physical absorbed radiation doses from each high-LET component. The total effective BNCT dose is then expressed as the sum of RBE-corrected physical absorbed doses with the unit Gray-equivalent (Gy-Eq).
Date: October 1, 1996
Creator: Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Fisher, C.D.; Bywaters, A.; Morris, G.M. et al.
Partner: UNT Libraries Government Documents Department

A Monte Carlo model system for core analysis and epithermal neutron beam design at the Washington State University Radiation Center

Description: The Monte Carlo Model System (MCMS) for the Washington State University (WSU) Radiation Center provides a means through which core criticality and power distributions can be calculated, as well as providing a method for neutron and photon transport necessary for BNCT epithermal neutron beam design. The computational code used in this Model System is MCNP4A. The geometric capability of this Monte Carlo code allows the WSU system to be modeled very accurately. A working knowledge of the MCNP4A neutron transport code increases the flexibility of the Model System and is recommended, however, the eigenvalue/power density problems can be run with little direct knowledge of MCNP4A. Neutron and photon particle transport require more experience with the MCNP4A code. The Model System consists of two coupled subsystems; the Core Analysis and Source Plane Generator Model (CASP), and the BeamPort Shell Particle Transport Model (BSPT). The CASP Model incorporates the S({alpha}, {beta}) thermal treatment, and is run as a criticality problem yielding, the system eigenvalue (k{sub eff}), the core power distribution, and an implicit surface source for subsequent particle transport in the BSPT Model. The BSPT Model uses the source plane generated by a CASP run to transport particles through the thermal column beamport. The user can create filter arrangements in the beamport and then calculate characteristics necessary for assessing the BNCT potential of the given filter want. Examples of the characteristics to be calculated are: neutron fluxes, neutron currents, fast neutron KERMAs and gamma KERMAs. The MCMS is a useful tool for the WSU system. Those unfamiliar with the MCNP4A code can use the MCMS transparently for core analysis, while more experienced users will find the particle transport capabilities very powerful for BNCT filter design.
Date: May 1, 1996
Creator: Burns, T.D. Jr.
Partner: UNT Libraries Government Documents Department

Optimization of the {sup 7}Li(p,n) proton beam energy for BNCT applications

Description: The reaction {sup 7}Li(p,n){sup 7} Be has been proposed as an accelerator-based source of neutrons for Boron Neutron Capture Therapy (BNCT). This reaction has a large steep resonance for proton energies of about 2.3 MeV which ends at about 2.5 MeV. It has generally been accepted that one should use 2.5 MeV protons to get the highest yield of neutrons for BNCT. This paper suggests that for BNCT the optimum proton energy may be about 2.3 MeV and that a proton energy of about 2.2 MeV will provide the same useful neutron fluence outside a thinner moderator as the neutron fluence from a 2.5 MeV proton beam with a thicker moderator.
Date: February 1, 1996
Creator: Bleuel, D.L. & Donahue, R.J.
Partner: UNT Libraries Government Documents Department

Target studies for accelerator-based boron neutron capture therapy

Description: Two new concepts, NIFTI and DISCOS, are described. These concepts enable the efficient production of epithermal neutrons for BNCT (Boron Neutron Capture Therapy) medical treatment, utilizing a low current, low energy proton beam impacting on a lithium target. The NIFTI concept uses an iron layer that strongly impedes the transmission of neutrons with energies above 24 KeV. Lower energy neutrons readily pass through this iron ``filter``, which has a deep ``window`` in its scattering cross section at 24 KeV. The DISCOS concept uses a rapidly rotating, high g disc to create a series of thin ({approximately} 1 micron thickness) liquid lithium targets in the form of continuous films through which the proton beam passes. The average energy lost by a proton as it passes through a single target is small, approximately 10 KeV. Between the targets, the proton beam is reaccelerated by an applied DC electric field. The DISCOS approach enables the accelerator -- target facility to operate with a beam energy only slightly above the threshold value for neutron production -- resulting in an output beam of low-energy epithermal neutrons -- while achieving a high yield of neutrons per milliamp of proton beam current.
Date: March 1, 1996
Creator: Powell, J.R.; Ludewig, H.; Todosow, M. & Reich, M.
Partner: UNT Libraries Government Documents Department

Boron neutron capture therapy of malignant brain tumors at the Brookhaven Medical Research Reactor

Description: Boron neutron capture therapy (BNCT) is a bimodal form of radiation therapy for cancer. The first component of this treatment is the preferential localization of the stable isotope {sup 10}B in tumor cells by targeting with boronated compounds. The tumor and surrounding tissue is then irradiated with a neutron beam resulting in thermal neutron/{sup 10}B reactions ({sup 10}B(n,{alpha}){sup 7}Li) resulting in the production of localized high LET radiation from alpha and {sup 7}Li particles. These products of the neutron capture reaction are very damaging to cells, but of short range so that the majority of the ionizing energy released is microscopically confined to the vicinity of the boron-containing compound. In principal it should be possible with BNCT to selectively destroy small nests or even single cancer cells located within normal tissue. It follows that the major improvements in this form of radiation therapy are going to come largely from the development of boron compounds with greater tumor selectivity, although there will certainly be advances made in neutron beam quality as well as the possible development of alternative sources of neutron beams, particularly accelerator-based epithermal neutron beams.
Date: December 31, 1996
Creator: Joel, D.D.; Coderre, J.A. & Chanana, A.D.
Partner: UNT Libraries Government Documents Department