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DOE OSTI2024

CD46-Targeted Theranostics for PET and 225 Ac-Radiopharmaceutical Therapy of Multiple Myeloma

Multiple myeloma is a plasma cell malignancy with an unmet clinical need for improved imaging methods and therapeutics. Recently, we identified CD46 as an overexpressed therapeutic target in multiple myeloma and developed the antibody YS5, which targets a cancer-specific epitope on this protein. We further developed the CD46-targeting PET probe [ 89 Zr]Zr-DFO-YS5 for imaging and [ 225 Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of prostate cancer. These prior studies suggested the feasibility of the CD46 antigen as a theranostic target in multiple myeloma. Herein, we validate [ 89 Zr]Zr-DFO-YS5 for immunoPET imaging and [ 225 Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of multiple myeloma in murine models. In vitro saturation binding was performed using the CD46 expressing MM.1S multiple myeloma cell line. ImmunoPET imaging using [ 89 Zr]Zr-DFO-YS5 was performed in immunodeficient (NSG) mice bearing subcutaneous and systemic multiple myeloma xenografts. For radioligand therapy, [ 225 Ac]Ac-DOTA-YS5 was prepared, and both dose escalation and fractionated dose treatment studies were performed in mice bearing MM1.S-Luc systemic xenografts. Tumor burden was analyzed using BLI, and body weight and overall survival were recorded to assess antitumor effect and toxicity. [ 89 Zr]Zr-DFO-YS5 demonstrated high affinity for CD46 expressing MM.1S multiple myeloma cells (K d = 16.3 nmol/L). In vitro assays in multiple myeloma cell lines demonstrated high binding, and bioinformatics analysis of human multiple myeloma samples revealed high CD46 expression. [ 89 Zr]Zr-DFO-YS5 PET/CT specifically detected multiple myeloma lesions in a variety of models, with low uptake in controls, including CD46 knockout (KO) mice or multiple myeloma mice using a nontargeted antibody. In the MM.1S systemic model, localization of uptake on PET imaging correlated well with the luciferase expression from tumor cells. A treatment study using [ 225 Ac]Ac-DOTA-YS5 in the MM.1S systemic model demonstrated a clear tumor volume and survival benefit in the treated groups. Our study showed that the CD46-targeted probe [ 89 Zr]Zr-DFO-YS5 can successfully image CD46-expressing multiple myeloma xenografts in murine models, and [ 225 Ac]Ac-DOTA-YS5 can effectively inhibit the growth of multiple myeloma. These results demonstrate that CD46 is a promising theranostic target for multiple myeloma, with the potential for clinical translation.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Conceptual Spacer Design for the ATR GEN I Target for Pu-238 Production in the Advanced Test Reactor at Idaho National Laboratory

The initial target design used for Pu-238 production at Idaho National Laboratory was designed by Oak Ridge National Laboratory to optimize the production of Pu-238 in the High Flux Isotope Reactor (HFIR) and are referred to as HFIR GEN II targets. To take advantage of the Advanced Test Reactor’s (ATR) taller active core region a redesign of the HFIR GEN II targets was needed. It was proposed to stack two HFIR GEN II targets nose to nose about the core center line; however, this resulted in excessive neutron and photon heating in the pellets located in the center. This peak heating was not desirable so three alternative designs were investigated for the ATR GEN I targets. The python-based code, MCNP to ORIGEN2 in Python (MOPY), was used to calculate the heating rates after 40 days of irradiation to capture the effects of each configuration. The purpose of this paper is to document the details of these conceptual design calculations and comparisons for the ATR GEN I targets.

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2020

Northstar Mo100 Target Beam Spot Size Sensitivity Study

Northstar Mo100 target for production of the medical isotope Mo99 is particularly sensitive to beam over focusing because of the intended high power density. At 38 MeV and 6.32 mA (240 kW beam power, nominally 160 kW th in the target), small deviation from the nominal 12 mm FWHM beam can significantly increase the target disk temperatures and more importantly the load bearing target window temperature. A rhodotron will be the source of the electron beam to be used in the isotope production. This machine operates in a pulsed beam mode, currently expected to be at 50 Hz, which results in a 100 C temperature oscillation above and below the steady state temperature that is the focus of this study. This must be considered in the determination of minimum beam spot size that can be accepted by the target without risk of failure. In addition to the nominal beam spot size of 12 mm, the analysis of 10, 11 and 14.5 mm beam spot sizes are analyzed. The primary conclusion is that an over focused beam to just 11 mm FWHM is the minimum beam spot allowable, based on window temperature and the Ultimate Tensile Stress (UTS) of the window material Inconel 718 as a function of temperature. In contrast an under focused beam of 14.5 mm FWHM has much reduced target and window temperatures, but there is a resulting 6% drop in isotope production, all other factor staying the same. These results are presented herein.

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2021

Post Examination of Candidate NpO 2 Targets for 238 Pu Production

Four targets composed of sintered NpO 2 pellets enclosed in Zircaloy cladding were irradiated in the High Flux Isotope Reactor for 2 to 4 cycles to determine if an oxide pellet and Zircaloy cladding would be usable candidates for 238 Pu production. The pellets were sintered to a high fraction of theoretical density (TD) and melt wires were placed in small holes that had been drilled in the center of selected pellets to determine if the pellet centers exceeded desirable operating temperatures. After irradiation, the targets were punctured to determine the internal target pressure and the fission gas release. None of the targets had excessive pressure, and fission gas release was in the range of 4 to 38%. The targets were then cut into segments for radiochemical analysis, and metallography (MET) mounts were created to examine the pellet microstructure and to search for the melt wires to determine if they had melted. Three of the four targets resulted in successful MET mounts; the two-cycle pellets were too friable to be handled. No signs of pellet melting were noted, and unfortunately, none of the melt wires could be recovered. The results indicate that this pellet/clad design offers a practical option for 238 Pu production.

36 MATERIALS SCIENCE↗

DOE OSTI2021

R&D toward design for a pion-production target for Mu2e-II

The Mu2e experiment at Fermilab will search for evidence of charged lepton flavor violation by observing the conversion of a negative muon into an electron in the Coulomb field of a nucleus without emission of neutrinos and will probe effective new-physics mass scales in the 103-104 TeV range. One of the main parts of the Mu2e experimental setup is its target station in which negative pions are generated in interactions of the 8 GeV primary proton beam with a tungsten target, which will be capable of producing $2\times10^{17}$ negative muons per year. Mu2e can be extended by a next generation experiment, Mu2e-II, with a sensitivity improved by another factor of 10 or more as enabled by the PIP-II accelerator upgrade project. PIP-II is a 250-meter-long linac capable of accelerating a 2 mA proton beam to a kinetic energy of 800 MeV corresponding to 1.6 MW of power. To achieve another factor of ten improvement in sensitivity, Mu2e-II will require about 100 kW of proton beam on target, and the added power requires a new target design. We will present our progress in RD of a target station conceptual design for Mu2e-II, using the MARS15 and G4beamline Monte-Carlo codes toward a selection between granular, conveyor, and rotating cylindrical target options.

Lynch, Kevin Richard↗

DOE OSTI2023

Simulating target tests at AP0 facility for Mu2e

The predicted production of muons and energy deposition for the production target of the Mu2e experiment are dependent on the documentation of cross-sections values, the properties of the target’s material, etc. Hence, making real tests on similar targets before its use on Mu2e will be a good indicator of the accuracy of the simulations done for the experiment. The main goal of the project is to simulate a target test at the AP0 Target Facility, previously used to create the muon beam for the Muon g-2 experiment. Results from these simulations will be used as input to engineering models of the target to produce predicted stress and surface temperature distributions, parameters that will later be measured in future beam runs to validate underlying cross section models.

Delgado, Amii Matamoros↗

DOE OSTI2023

Secondary Pion Production using the LINAC Beam on Graphite and Tungsten Targets

The Fermilab 400-MeV Linac primary proton beam can produce precision, single-species secondary beams using a production target in the MeV Test Area experimental hall; specifically, pions from 4 up to 120 MeV kinetic energy. (These low energy pions rapidly decay into a muon beam in a secondary collection and transport beamline.) Although graphite is a standard production target material given its ultra-high temperature tolerance and low impact on the post-target primary beam, secondary pion/muon total production cross sections increase approximately as Z1/3 for positive muons and N2/3 for negative muons. Higher mass targets such as tungsten can potentially increase low-energy m+ and m- rates by factors of 3 and 8, respectively. Initial production studies have confirmed higher muon yield from heavy targets (tungsten vs carbon), but also, surprisingly, show significant differences in pion production between modern hadronic models (GENIEhad) and between GEANT and MCNP, state of the art production modeling codes. This project will further investigate the production discrepancies between these two target materials and between different physics models with high-statistics runs using the GEANT-based code, G4Beamline to better quantify the results and compare with production data which will be obtained using the MTA secondary beamline.

Ahmed, Shiza↗

DOE OSTI2024

Nuclear imaging to diagnose and correct target-driver registration at high-repetition-rate for improved reactor efficiency

Inertial Confinement Fusion produces energy from a burning plasma lasting a fraction of a nanosecond. Power plant designs based on Inertial Fusion Energy (IFE) will need to ignite targets 1-10 times a second, fired as projectiles into a chamber and delivering the driver to the target location. Driver asymmetry is known to impact ICF experiments at gain near unity and remains a candidate for primary yield degradation, and therefore fusion power plant energy output, for high-gain target designs. For a Fusion Power Plant (FPP), continuous and real-time monitoring of target performance provides an opportunity to stabilize or correct the target-driver registration. This requires x-ray and neutron imaging with a large field-of-view, sufficiently high resolution, fast analysis and to subtend a minimal solid angle. We introduce design criteria for such an imaging system that uses a coded aperture and time-gated, lens-coupled scintillators as a viable solution and outline the research steps required to field such a system. Integrating the imaging system into an IFE power plant as part of an active feedback loop could increase average power output by reducing the failure rate due to mis-aligned drivers with respect to the target.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2024

Three-dimensional simulations of magneto-inertial Magnetic-Direct-Drive targets

For the cylindrically symmetric targets that are normally fielded on the Z machine, two dimensional axisymmetric MHD simulations provide the backbone of our target design capability. These simulations capture the essential operation of the target and allow for a wide range of physics to be addressed at a substantially lower computational cost than 3D simulations. This approach, however, makes some approximations that may impact its ability to accurately provide insight into target operation. As an example, in 2D simulations, targets are able to stagnate directly to the axis in a way that is not entirely physical, leading to uncertainty in the impact of the dynamical instabilities that are an important source of degradation for ICF concepts. In this report, we have performed a series of 3D calculations in order to assess the importance of this higher fidelity treatment on MagLIF target performance.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2024

Multiphysics Simulations of Nanofibrous High Power Targets for the Inference of Failure Modes

Fermilab s High Power Targetry Research and Development (HPT R&D) group have been developing and studying an electrospun nanofiber target concept to support the need for robust targets in future fixed target facilities. These nanofiber mats have demonstrated resistance to radiation damage, and the free motion of the individual fibers is expected to mitigate the cyclic stresses induced by a pulsed, high-power beam. To evaluate the efficacy of this concept, nanofiber mat samples have been sent by the HPT R&D group to the HiRadMat facility at CERN for prototypic thermal shock testing; the outcomes of these experiments show that the survivability of a nanofiber target depends on its construction parameters, in particular the packing density of the fibers. Samples with higher packing densities have consistently been destroyed by exposure to the HiRadMat beam, with a hole at the beam center visible, and layers of nanofibers peeled away from the center hole, whereas samples with lower densities have survived with limited damage. The exact reason for the failure of the higher density targets was unclear at the time of the original experiments, but the results of our recent multiphysics simulations which recreate the experiments support the hypothesis that the expansion and pressurization of the air inside the target after being heated by the pulsed beam is the cause; in a high density nanofiber mat, the motion of air through the pores of the mat is much more restricted, and induces a larger pressure on the fibers, blowing the mat apart. In this talk, we ll share the results of these simulations and discuss how they support this hypothesis.

Asztalos, Will↗

DOE OSTI2024

Fabrication of a Point-Like Transmission Target for Reducing Computed Tomography Imaging Artifacts

In this study, we address the challenge of enhancing image quality and spatial resolution in computed tomography (CT) imaging by introducing simulation and fabrication of high aspect ratio, point-like transmission targets. Utilizing advanced electroplating techniques, traditionally employed in the fabrication of Through Substrate Via (TSV) interconnects for CMOS circuitry, we successfully embed copper targets within silicon substrates. This method allows us to create high-aspect-ratio features specifically designed for X-ray transmission targets, resulting in micro targets that exhibit a volume increase compared to conventional evaporated surface targets. Furthermore, we present simulation results of the X-ray spectrum generated by these targets, demonstrating their potential to significantly improve both image quality and spatial resolution in CT applications. Our findings suggest that leveraging advanced fabrication techniques can open new avenues for the development of enhanced imaging technologies in medical diagnostics and beyond.

47 OTHER INSTRUMENTATION↗

DOE OSTI2025

Methodology to Establish Performance Targets for Building Energy Codes

This report explains the underlying development of the U.S. NZE building sector performance targets reported in Federal Register Notice XX. This document also includes NZE performance targets for U.S. states, which were developed following the same procedures used to develop the national values. These national and state targets are intended to support the establishment and attainment of NZE goals over time. Where residential and commercial building energy code compliance mechanisms apply to new buildings and major renovations and dictate performance requirements, these targets reflect the recommended, minimum levels of performance. Appendix A provides the performance values and targets by U.S. state for residential and commercial buildings. These include each state’s adopted energy code performance, current published MEC performance value, and a nominal NZE code compliance performance target. The current code and NZE values can be compared to the state adopted code value to indicate the level of advancement needed to move towards recommended NZE building performance levels. Additional supplemental resources are available to support states and local governments ready to move from setting NZE policy goals to adopting NZE codes. More information about these resources and the actions states can take to achieve NZE buildings with energy codes are provided in the body of this document.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

DOE OSTI2022

R-Value Measurements Performed on Actinide Targets Irradiated using the GODIVA IV Critical Assembly in FY22

The separation and characterization of two irradiated uranium targets, a depleted uranium (DU) and a highly enriched uranium (HEU) target as well as a plutonium (Pu) target, was conducted in April of 2022. The three targets were assembled at Los Alamos National Laboratory (LANL) and irradiated using the GODIVA critical assembly at the National Criticality Experiments Research Center (NCERC). Splits of the dissolved targets were received by Pacific Northwest National Laboratory (PNNL) after which the PNNL and LANL teams chemically separated the solutions using independent separation schemes and analyzed the separated fractions for short lived actinides and fission products. Chemical separations were traced with stable or radioactive tracers to allow for the determination of chemical yields, analyzing using either inductively coupled plasma optical emission spectroscopy (ICP-OES), inductively coupled plasma mass spectrometry (ICP-MS) or gamma emission analysis (GEA) depending on the nature of the tracer. The Pu target solution was traced with stable elements at LANL to follow elemental fractionation during a Pu removal step. Many analytical techniques were used by PNNL including kinetic phosphorescence analysis (KPA), ICP-OES, ICP-MS, GEA, and thermal ionization mass spectrometry (TIMS) depending on the analyte’s need.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2026

Prediction of non-intuitive metabolic targets with bayesian metabolic control analysis to improve 3-hydroxypropionic acid production in Aspergillus niger

Development of efficient bioconversion processes is limited by the ability to predictably improve metabolic flux. Here we deployed Bayesian Metabolic Control Analysis as a platform to integrate multi-omics data with metabolic modeling and evaluated its ability to predict genetic interventions that improve metabolic flux. Global Metabolomics and proteomics data was collected from 17 Aspergillus niger strains engineered to produce the platform biochemical 3-hydroxypropionic acid from which seven actional genetic interventions were predicted from significant flux control coefficients. Of the suggested genetic interventions, two were present within the intuitively designed strains used for training (malonic semialdehyde dehydrogenase and pyruvate carboxylase) while five predicted targets were present within non-intuitive areas of the metabolic network including 5-formyltetrahydrofolate deformylase and four mitochondrial enzymes, alcohol dehydrogenase, succinyl-CoA ligase, aspartate aminotransferase, and malate dehydrogenase. Six of the targets were validated in the highest performing 3-HP strain used for multi-omics data generation which contained a prior disruption of the highest scoring target malonic semialdehyde dehydrogenase. Predicted directional perturbation of five of the six tested targets significantly improved titer and rate of 3-HP production and two significantly improved yield. The greatest improvements were observed following disruption of the non-intuitive target succinyl-CoA ligase which increased titer by 39% and yield by 29% (to 20.4 g/L 3-HP and 0.31 g 3-HP/g glucose) over the strains used for training. This study demonstrates the utility of Bayesian Metabolic Control Analysis and highlights the ability to predict meaningful genetic targets in unexpected areas of metabolism to improve engineered strains for bioconversion.

3-hydroxypropionic acid↗

NASA NTRS1973

A computer program to determine the possible daily release window for sky target experiments

A computer program is presented which is designed to determine the daily release window for sky target experiments. Factors considered in the program include: (1) target illumination by the sun at release time and during the tracking period; (2) look angle elevation above local horizon from each tracking station to the target; (3) solar depression angle from the local horizon of each tracking station during the experimental period after target release; (4) lunar depression angle from the local horizon of each tracking station during the experimental period after target release; and (5) total sky background brightness as seen from each tracking station while viewing the target. Program output is produced in both graphic and data form. Output data can be plotted for a single calendar month or year. The numerical values used to generate the plots are furnished to permit a more detailed review of the computed daily release windows.

Michaud, N. H.↗

NASA NTRS1979

OPS MCC level B/C formulation requirements: Area targets and space volumes processor

The level B/C mathematical specifications for the area targets and space volumes processor (ATSVP) are described. The processor is designed to compute the acquisition-of-signal (AOS) and loss-of-signal (LOS) times for area targets and space volumes. The characteristics of the area targets and space volumes are given. The mathematical equations necessary to determine whether the spacecraft lies within the area target or space volume are given. These equations provide a detailed model of the target geometry. A semianalytical technique for predicting the AOS and LOS time periods is disucssed. This technique was designed to bound the actual visibility period using a simplified target geometry model and unperturbed orbital motion. Functional overview of the ATSVP is presented and it's detailed logic flow is described.

Bishop, M. J., Jr.↗

NASA NTRS1980

Radar target for remotely sensing hydrological phenomena

An apparatus for remotely measuring and accessing water status relative to snow and glacial melt, surface runoff, rainfall, evaporation, flow rate, and soil moisture is described. A radar target located at a selected location on the surface of the Earth is designed to collect water and render its cross sectional area variable as a function of the height of the water level within the target. The target is remotely monitored by an orbiting or airborne synthetic aperature radar. The target appears as a bright spot embedded within the radar image. The target brightness is indicative of the height of the water level within the ground located target.

Sivertson, W. E., Jr.↗

NASA NTRS1988

Infrared retroreflecting lidar calibration target

A lightweight flexible lidar calibration target has been fabricated for use at 10.6 microns. The biconical reflectance of the target was kept low to reduce the possiblity of detector saturation. The target has been designed so that the biconical reflectance is nearly independent of the target orientation over the range of angles of incidence + or - 60 deg, causing the calibration properties to be independent of target orientation. The present target is relatively inexpensive to construct.

Lea, T. K.↗