Engineering topics

Nigg, David W

Publications and source records attributed to Nigg, David W.

10 records

DOE OSTI2012

Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA–BNCT, boronophenylalanine (BPA) ? neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA–BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks posttreatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA–BNCT, 2.7 ± 1.8 for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mgfell significantly to 19 ± 16 mg for BPA–BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA–BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA– BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2012

Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2012

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2012

IMPROVED COMPUTATIONAL NEUTRONICS METHODS AND VALIDATION PROTOCOLS FOR THE ADVANCED TEST REACTOR

The Idaho National Laboratory (INL) is in the process of modernizing the various reactor physics modeling and simulation tools used to support operation and safety assurance of the Advanced Test Reactor (ATR). Key accomplishments so far have encompassed both computational as well as experimental work. A new suite of stochastic and deterministic transport theory based reactor physics codes and their supporting nuclear data libraries (HELIOS, KENO6/SCALE, NEWT/SCALE, ATTILA, and an extended implementation of MCNP5) has been installed at the INL. Corresponding models of the ATR and ATRC are now operational with all five codes, demonstrating the basic feasibility of the new code packages for their intended purpose. Of particular importance, a set of as-run core depletion HELIOS calculations for all ATR cycles since August 2009 was successfully completed during 2011. This demonstration supported a decision late in the year to proceed with the phased incorporation of the HELIOS methodology into the ATR fuel cycle management process beginning in 2012. On the experimental side of the project, new hardware was fabricated, measurement protocols were finalized, and the first four of six planned physics code validation experiments based on neutron activation spectrometry were conducted at the ATRC facility. Data analysis for the first three experiments, focused on characterization of the neutron spectrum in one of the ATR flux traps, has been completed. The six experiments will ultimately form the basis for a flexible, easily-repeatable ATR physics code validation protocol that is consistent with applicable ASTM standards.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

DOE OSTI2011

Boron Neutron Capture Therapty (BNCT) in an Oral Precancer Model: Therapeutic Benefits and Potential Toxicity of a Double Application of BNCT with a Six-Week Interval

Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10 + BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB- 10 + BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10 + BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2011

COMBINE7.1 - A Portable ENDF/B-VII.0 Based Neutron Spectrum and Cross-Section Generation Program

COMBINE7.1 is a FORTRAN 90 computer code that generates multigroup neutron constants for use in the deterministic diffusion and transport theory neutronics analysis. The cross-section database used by COMBINE7.1 is derived from the Evaluated Nuclear Data Files (ENDF/B-VII.0). The neutron energy range covered is from 20 MeV to 1.0E-5 eV. The Los Alamos National Laboratory NJOY code is used as the processing code to generate a 167 fine-group cross-section library in MATXS format for Bondarenko self-shielding treatment. Resolved resonance parameters are extracted from ENDF/B-VII.0 File 2 for a separate library to be used in an alternate Nordheim self-shielding treatment in the resolved resonance energy range. The equations solved for energy dependent neutron spectrum in the 167 fine-group structure are the B3 or B1 zero-dimensional approximations to the transport equation. The fine group cross sections needed for the spectrum calculation are first prepared by Bondarenko self-shielding interpolation in terms of background cross section and temperature. The geometric lump effect, when present, is accounted for by augmenting the background cross section. Nordheim self-shielded fine group cross sections for a material having resolved resonance parameters overwrite correspondingly the existing self-shielded fine group cross sections when this option is used. COMBINE7.1 coalesces fine group cross sections into broad group macroscopic and microscopic constants. The coalescing is performed by utilizing fine-group fluxes and/or currents obtained by spectrum calculation as the weighting functions. The multigroup constants may be output in any of several standard formats including INL format, ANISN 14** free format, CCCC ISOTXS format, and AMPX working library format. ANISN-PC, a one-dimensional (1-D) discrete-ordinate transport code, is incorporated into COMBINE7.1. As an option, the 167 fine-group constants generated by zero-dimensional COMBINE portion in the program can be used to calculate regionwise spectra in the 1-D ANISN portion, all internally to reflect the 1-D transport correction. The regionwise spectra are then used to generate mutigroup regionwise neutron constants. The 1-D neutron transport can be performed up to three stages, e.g., from a TRISO fuel to PEBBLE to 1-D full core wedge. In addition, COMBINE7.1 has now the capability of adjoint flux calculation through the 1-D ANISN transport. Photon transport capability is also added. For this, a photon production and photo-atomic cross section library, MATNG.LIB, was generated in MATXS format through NJOY code. The photon production cross section matrix is of 167 neutron - 18 photon groups. Photo-atomic cross sections, including heating, are in 18 energy groups.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2011

A Feasibility Study to Determine Cooling Time and Burnup of ATR Fuel Using a Nondestructive Technique and Three Types of Gamma-ray Detectors

A Feasibility Study to Determine Cooling Time and Burnup of ATR Fuel Using a Nondestructive Technique1 Rahmat Aryaeinejad, Jorge Navarro, and David W Nigg Idaho National Laboratory Abstract Effective and efficient Advanced Test Reactor (ATR) fuel management require state of the art core modeling tools. These new tools will need isotopic and burnup validation data before they are put into production. To create isotopic, burn up validation libraries and to determine the setup for permanent fuel scanner system a feasibility study was perform. The study consisted in measuring short and long cooling time fuel elements at the ATR canal. Three gamma spectroscopy detectors (HPGe, LaBr3, and HPXe) and two system configurations (above and under water) were used in the feasibility study. The first stage of the study was to investigate which detector and system configuration would be better suited for different scenarios. The second stage of the feasibility study was to create burnup and cooling time calibrations using experimental isotopic data collected and ORIGEN 2.2 burnup data. The results of the study establish that a better spectra resolution is achieve with an above the water configuration and that three detectors can be used in the permanent fuel scanner system for different situations. In addition it was conclude that a number of isotopic ratios and absolute measurements could be used to predict ATR fuel burnup and cooling times. 1This work was supported by the U.S. Depart¬ment of Energy (DOE) under Battelle Energy Alliance, LLC Contract No. DE-AC07-05ID14517.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

DOE OSTI2011

"Sequential” Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10B carriers in tumors followed by irradiation with a thermal or epithermal neutron beam. The minor abundance stable isotope of boron, 10B, interacts with low energy (thermal) neutrons to produce high linear energy transfer (LET) a-particles and 7Li ions. These disintegration products are known to have a high relative biological effectiveness (RBE). Their short range (<10 {micro}m) would limit the damage to cells containing 10B (1,2). Thus, BNCT would target tumor tissue selectively, sparing normal tissue. Clinical trials of BNCT for the treatment of glioblastoma multiforme and/or melanoma and, more recently, head and neck tumors and liver metastases, using boronophenylalanine (BPA) or sodium mercaptoundecahydrododecaborane (BSH) as the 10B carriers, have been performed or are underway in Argentina, Japan, the US and Europe (e.g. 3-8). To date, the clinical results have shown a potential, albeit inconclusive, therapeutic advantage for this technique. Contributory translational studies have been carried out employing a variety of experimental models based on the implantation of tumor cells in normal tissue (e.g. 5).

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

DOE OSTI2011

Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2010

Next Generation Nuclear Plant Methods Technical Program Plan

One of the great challenges of designing and licensing the Very High Temperature Reactor (VHTR) is to confirm that the intended VHTR analysis tools can be used confidently to make decisions and to assure all that the reactor systems are safe and meet the performance objectives of the Generation IV Program. The research and development (R&D) projects defined in the Next Generation Nuclear Plant (NGNP) Design Methods Development and Validation Program will ensure that the tools used to perform the required calculations and analyses can be trusted. The Methods R&D tasks are designed to ensure that the calculational envelope of the tools used to analyze the VHTR reactor systems encompasses, or is larger than, the operational and transient envelope of the VHTR itself. The Methods R&D focuses on the development of tools to assess the neutronic and thermal fluid behavior of the plant. The fuel behavior and fission product transport models are discussed in the Advanced Gas Reactor (AGR) program plan. Various stress analysis and mechanical design tools will also need to be developed and validated and will ultimately also be included in the Methods R&D Program Plan. The calculational envelope of the neutronics and thermal-fluids software tools intended to be used on the NGNP is defined by the scenarios and phenomena that these tools can calculate with confidence. The software tools can only be used confidently when the results they produce have been shown to be in reasonable agreement with first-principle results, thought-problems, and data that describe the “highly ranked” phenomena inherent in all operational conditions and important accident scenarios for the VHTR.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗