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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Global Issues of Radiopharmaceutical Access and Availability: a Nuclear Medicine Global Initiative Project

The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging by supporting the practice and application of nuclear medicine. The first project focused on standardization of administered activities in pediatric nuclear medicine and resulted in two manuscripts. For its second project the NMGI chose to explore issues impacting on access and availability of radiopharmaceuticals around the world. Methods: Information was obtained by survey responses from 35 countries on available radioisotopes, radiopharmaceuticals and kits for diagnostic and therapeutic use. Issues impacting on access and availability of radiopharmaceuticals in individual countries were also identified. Results: Detailed information on radiopharmaceuticals utilized in each country, and sources of supply, was evaluated. Responses highlighted problems in access particularly due to the reliance on a sole provider, regulatory issues and reimbursement, as well as issues of facilities and workforce particularly in low- and middle-income countries. Conclusion: Finally, strategies to address access and availability of radiopharmaceuticals are outlined, to enable timely and equitable patient access to nuclear medicine procedures worldwide. In the face of disruptions to global supply chains by the COVID-19 outbreak, renewed focus on ensuring reliable supply of radiopharmaceuticals is a major priority for nuclear medicine practice globally.

43 PARTICLE ACCELERATORS↗
DOE OSTI2020

Radioarsenic: A promising theragnostic candidate for nuclear medicine

Molecular imaging is a non-invasive process that enable the visualization, characterization, and quantitation of biological processes at the molecular and cellular level. With the emergence of theragnostic agents to diagnose and treat disease for personalized medicine there is a growing need for matched pairs of isotopes. Matched pairs offer the unique opportunity to obtain patient specific information from SPECT or PET diagnostic studies to quantitate in vivo function or receptor density to inform and tailor therapeutic treatment. There are several isotopes of arsenic that have emissions suitable for either or both diagnostic imaging and radiotherapy. Their half-lives are long enough to pair them with peptides and antibodies which take longer to reach maximum uptake to facilitate improved patient pharmacokinetics and dosimetry then can be obtained with shorter lived radionuclides. Arsenic-72 even offers availability from a generator that can be shipped to remote sites and thus enhances availability. Arsenic has a long history as a diagnostic agent, but until recently has suffered from limited availability, lack of suitable chelators, and concerns about toxicity have inhibited its use in nuclear medicine. However, new production methods and novel chelators are coming online and the use of radioarsenic in the pico and nanomolar scale is well below the limits associated with toxicity. This manuscript will review the production routes, separation chemistry, radiolabeling techniques and in vitro/in vivo studies of three medically relevant isotopes of arsenic (arsenic-74, arsenic-72, and arsenic-77).

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2023

Reining in Radium for Nuclear Medicine: Extra-Large Chelator Development for an Extra-Large Ion

Targeted α therapy (TAT) of soft-tissue cancers using the α particle-emitting radionuclide 223 Ra holds great potential because of its favorable nuclear properties, adequate availability, and established clinical use for treating metastatic prostate cancer of the bone. Despite these advantages, the use of 223 Ra has been largely overshadowed by other α emitters due to its challenging chelation chemistry. A key criterion that needs to be met for a radionuclide to be used in TAT is its stable attachment to a targeting vector via a bifunctional chelator. The low charge density of Ra 2+ arising from its large ionic radius weakens its electrostatic binding interactions with chelators, leading to insufficient complex stability in vivo. In this study, we synthesized and evaluated macropa-XL as a novel chelator for 223 Ra. It bears a large 21-crown-7 macrocyclic core and two picolinate pendent groups, which we hypothesized would effectively saturate the large coordination sphere of the Ra 2+ ion. The structural chemistry of macropa-XL was first established with the nonradioactive Ba 2+ ion using X-ray diffraction and X-ray absorption spectroscopy, which revealed the formation of an 11-coordinate complex in a rare anti pendent-arm configuration. Subsequently, the stability constant of the [Ra(macropa-XL)] complex was determined via competitive cation exchange with 223 Ra and 224 Ra radiotracers and compared with that of macropa, the current state-of-the-art chelator for Ra 2+ . A moderate log K ML value of 8.12 was measured for [Ra(macropa-XL)], which is approximately 1.5 log K units lower than the stability constant of [Ra(macropa)]. This relative decrease in Ra 2+ complex stability for macropa-XL versus macropa was further probed using density functional theory calculations. Additionally, macropa-XL was radiolabeled with 223 Ra, and the kinetic stability of the resulting complex was evaluated in human serum. Furthermore, although macropa-XL could effectively bind 223 Ra under mild conditions, the complex appeared to be unstable to transchelation. Collectively, this study sheds additional light on the chelation chemistry of the exotic Ra 2+ ion and contributes to the small, but growing, number of chelator development efforts for 223 Ra-based TAT.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Molybdenum-99 from Molten Salt Reactor as a Source of Technetium-99m for Nuclear Medicine: Past, Current, and Future of Molybdenum-99

Technitium-99m ( 99m Tc), a widely used radioisotope, is used in tens of millions of medical diagnostic procedures annually. However, it is hard to store and must be immediately used upon production due to its short half-life (i.e., 6 h); thus, it is currently produced from 99 Mo, which itself is a result of 235 U fission. The majority of 99 Mo supplies to U.S. patients are currently provided by foreign producers and produced using highly enriched uranium (HEU). In order to minimize the proliferation risks of HEU-based medical isotope production, the U.S. Department of Energy’s National Nuclear Security Administration has funded a program to accelerate the development of technologies to produce 99 Mo without the use of HEU. Today, the global supply of 99 Mo depends on a limited number of nuclear reactors, and production has been interrupted unexpectedly since 2009 due to the fleet’s advanced age. Herein, alternative options for 99 Mo production are discussed, and one potential option is to obtain 99m Tc from molten salt reactors (MSRs). A MSR is a nuclear fission reactor that can operate at or close to atmospheric pressure with liquid fuel, which allows for producing isotopes in a timely manner. In this paper, the past and current production of 99 Mo via nuclear reactors is described, and the future of 99 Mo production by MSRs is discussed. The behavior and chemical properties of molybdenum in fluoride salts in MSRs and the possible extraction methods are also examined in addition to the limitation of current studies.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
DOE OSTI2022

Radiochemistry and nuclear chemistry workforce in the United States

The disciplines of radiochemistry and nuclear chemistry have direct applications in the fields of national security, nuclear medicine, nuclear power production, and environmental management. Although, often, nuclear and radiochemistry are grouped together and many experts work in both areas, the definition for each field is slightly different. For example, radiochemistry may be defined as the application of the phenomena of radioactive decay and techniques common to nuclear physics so as to solve problems in the field of chemistry. In contrast, nuclear chemistry may be defined as the application of procedures and techniques common to chemistry to study the structure of the atomic nucleus. This chapter provides a brief update of the current state of, and critical U.S. needs for, nuclear chemistry and radiochemistry expertise as the Assuring a Future U.S.-Based Nuclear and Radiochemistry Expertise report was published by National Academy of Sciences (NAS) in 2012.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2022

New Apparatus for Neutron Capture Measurements on Extra Small Radioactive Samples: The DICER Instrument at LANSCE

We report the neutron capture cross section, the probability per unit area a neutron is absorbed by a nucleus followed by the emission of gamma ray(s), is an important quantity in several fields such as astrophysics, nuclear criticality safety, radiochemical diagnostics, nuclear medicine, nuclear forensics and nuclear security. Accurate knowledge of how neutrons interact with matter is a crucial component to understand physical processes in depth. A great example is the understanding of how our universe was created, a quest that requires accurate modeling in which neutron capture cross sections are a key ingredient

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2023

Laser-driven production with advanced targets of Copper-64 for medical applications

Radionuclides are of paramount importance in nuclear medicine both for clinical uses and radiopharmaceutical production. Among the others, nuclides suitable for theranostics like Copper-64 are particularly attractive since they can play both a diagnostic and therapeutic role. In the last years, the growing demand for these nuclides stimulated the research of new solutions, along with cyclotrons already in use, for their production. In this respect, a promising alternative is laser-driven proton accelerators based on the interaction of superintense laser pulses with target materials. Because of their potential compactness and flexibility, they are under investigation for several applications ranging from materials science to nuclear medicine. Moreover, the use of advanced Double-Layer targets (DLTs) was identified as a viable route to increase the number and energy of the accelerated protons to satisfy the requirements of demanding applications. In this contribution, we numerically investigate the use of DLT-based laser-driven sources for Copper-64 production. We show that activities relevant to pre-clinical studies can be achieved with an existing 150 TW laser and DLTs. Moreover, we extend the discussion by considering a broad range of laser systems by exploiting a theoretical model. Our results can guide the choice of laser and target parameters for future experimental investigations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

A Framework for Patient-Centered Pathways of Care for Radiopharmaceutical Therapy: An ASTRO Consensus Document

Radiopharmaceutical therapy (RPT) is an area of projected growth and importance with several agents in clinical use, new agents in late-phase clinical trials, and many others under testing and development. This article proposes a framework for developing pathways of care that can be broadly applied to all RPTs, representing the current status of RPT. It suggests foundational elements for many pathways of care for patients with cancer and concludes with areas in active development and the future horizon for RPT treatment centers. Developing a framework for patient-centered pathways of care is a critical step in establishing RPT as standard therapy for patients with a diverse spectrum of cancers. This expected increase in RPT treatment options will affect a much larger population of patients with complex cancer. It will also require enhanced coordination and collaboration among appropriately qualified personnel with diverse expertise in image acquisition, image interpretation, quantitative imaging, dosimetry calculation, radiation quality assurance and safety as well as oncology care and RPT-induced sequelae and response assessment. The essential role of this evolving RPT care team within multidisciplinary oncology care is a cornerstone of this framework for a patient-centered pathway of care for RPT. Given the status of current RPT practice and the horizon for future applications, this patient-centered pathway of care guidance is timely and should help inform future clinical RPT practice paradigms. A task force was recruited from the Theranostic Working Group of the American Society for Radiation Oncology (ASTRO) in May 2019 with equal representation from the nuclear medicine community. The task force expanded on a framework that was originally conceived by the Working Group for patient-centered care. This framework was developed to incorporate the strengths of both radiation oncologists and nuclear medicine physicians. The manuscript was then developed by the task force and posted on the ASTRO website for a 6-week public comment period ending in July 2020. Comments were adjudicated, and the draft was sent to external organizations for potential endorsement. This document was sent to the ASTRO Board of Directors in October 2020 for approval.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Friends or Foes: Fundamental Principles of Th-Organic Scaffold Chemistry Using Zr-Analogs as a Guide

The fundamental interest in actinide chemistry, particularly for the development of thorium-based materials, is experiencing a renaissance owing to the recent and rapidly growing attention to fuel cycle reactors, radiological daughters for nuclear medicine, and efficient nuclear stockpile development. Herein, we uncover fundamental principles of thorium chemistry on the example of Th-based extended structures such as metal–organic frameworks in comparison with the discrete systems and zirconium extended analogs, demonstrating remarkable over two-and-half-year chemical stability of Th-based frameworks as a function of metal node connectivity, amount of defects, and conformational linker rigidity through comprehensive spectroscopic and crystallographic analysis as well as theoretical modeling. Despite exceptional chemical stability, we report the first example of studies focusing on the reactivity of the most chemically stable Th-based frameworks in comparison with the discrete Th-based systems such as metal–organic complexes and a cage, contrasting multicycle recyclability and selectivity (>97%) of the extended structures in comparison with the molecular compounds. Altogether, the presented work not only establishes the conceptual foundation for evaluating the capabilities of Th-based materials but also represents a milestone for their multifaceted future and foreshadows their potential to shape the next era of actinide chemistry.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Chelating Rare-Earth Metals (Ln 3+ ) and 225 Ac 3+ with the Dual-Size-Selective Macrocyclic Ligand Py 2 -Macrodipa

Radioisotopes of metallic elements, or radiometals, are widely employed in both therapeutic and diagnostic nuclear medicine. For this application, chelators that efficiently bind the radiometal of interest and form a stable metal–ligand complex with it are required. Toward the development of new chelators for nuclear medicine, we recently reported a novel class of 18-membered macrocyclic chelators that is characterized by their ability to form stable complexes with both large and small rare-earth metals (Ln 3+ ), a property referred to as dual size selectivity. A specific chelator in this class called py-macrodipa, which contains one pyridyl group within its macrocyclic core, was established as a promising candidate for 135 La 3+ , 213 Bi 3+ , and 44 Sc 3+ chelation. Building upon this prior work, here we report the synthesis and characterization of a new chelator called py 2 -macrodipa with two pyridyl units fused into the macrocyclic backbone. Its coordination chemistry with the Ln 3+ series was investigated by NMR spectroscopy, X-ray crystallography, density functional theory (DFT) calculations, analytical titrations, and transchelation assays. These studies reveal that py 2 -macrodipa retains the expected dual size selectivity and possesses an enhanced thermodynamic affinity for all Ln 3+ compared to py-macrodipa. By contrast, the kinetic stability of Ln 3+ complexes with py 2 -macrodipa is only improved for the light, large Ln 3+ ions. Based upon these observations, we further assessed the suitability of py 2 -macrodipa for use with 225 Ac 3+ , a large radiometal with valuable properties for targeted α therapy. Radiolabeling and stability studies revealed py 2 -macrodipa to efficiently incorporate 225 Ac 3+ and to form a complex that is inert in human serum over 3 weeks. Although py 2 -macrodipa does not surpass the state-of-the-art chelator macropa for 225 Ac 3+ chelation, it does provide another effective 225 Ac 3+ chelator. Furthermore, these studies shed light on the fundamental coordination chemistry of the Ln 3+ series and may inspire future chelator design efforts.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Improved age- and gender-specific radiation risk models applied on cohorts of Swedish patients

The aim of this study is to implement lifetime attributable risk (LAR) predictions for radiation induced cancers for Swedish cohorts of patients of various age and sex, undergoing diagnostic investigations by nuclear medicine methods. Methods: Calculations are performed on Swedish groups of patients with Paget's disease and with bone metastases from prostatic cancer and diagnosed with bone scintigraphy with an administration of 500 MBq 99m Tc-phosphonate. Results: The inclusion of patient survival rates into the calculations lowers the induced radiation cancer risk, as it takes into account that cohorts of patients have shorter predicted survival times than the general population. Conclusion: LAR estimations could be valuable for referring physicians, nuclear medicine physicians, nurses, medical physicists, radiologists, and oncologists and as well as ethical committees for risk estimates for specific subgroups of patients. Caution is however advised with respect to application of LAR predictions to individuals (because of individual sensitivities, circumstances, etc.).

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2020

Thermal Process Technology for Nuclear Applications - 20379

ANSTO's Synroc technology has been developed to provide a safe, secure matrix for the immobilization and final disposal of radioactive waste. Synroc technology will be used to manage radioactive wastes from the production of the radioisotope Molybdenum-99 (Mo-99). This paper shall outline various stages of the process development with specific reference to the thermal treatment technology of calcination. Calcination is a key step in the Synroc process [1-2].The rotary thermal processing system includes: an advanced heating element design for increased robustness and ease of remote operation and maintenance, an enhanced modular design of components for ease of remote maintenance in a hot cell and in compliance with hot cell radioactive environment requirements for safety, reliability and maintainability. In addition to thermal treatment of waste from nuclear medicine production, this technology provides solutions for a variety of nuclear materials processing applications including sintering UO{sub 2} pellets for reactor fuel rods, oxidation of UO{sub 2} pellets, swarf, and powder to U{sub 3}O{sub 8}, de-nitration of Uranyl nitrate and hydrofluorination of UO{sub 2} pellets. The paper will also discuss thermal processing solutions for a range of nuclear applications. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2020

American Chemical Society's summer school in nuclear and radiochemistry. Final report

The ACS Summer Schools in Nuclear and Radiochemistry (herein called “Summer Schools”) were held each year at San Jose State University (SJSU) and Brookhaven National Laboratory (BNL). The Summer Schools are an intensive, six-week program that includes both a lecture component covering fundamental principles of nuclear chemistry and radiochemistry and a laboratory component providing hands-on experience for the students to observe and test many of the basic principles that they learn about in lecture and in the special seminars. Each site hosts 12 undergraduate students annually. Participants are selected from a nation-wide pool of applicants who are currently enrolled as undergraduates seeking bachelors’ degrees, preferably in disciplines of physical sciences or engineering. To broaden the students’ perspectives on nuclear science, prominent research scientists active in nuclear and/or radiochemical research participate in a Guest Lecture Series. Symposia emphasizing nuclear security, nuclear medicine, and career opportunities are conducted as a part of the program.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2025

Synthesis of DOTA-Based 43 Sc Radiopharmaceuticals Using Cyclotron-Produced 43 Sc as Exemplified by [ 43 Sc]Sc-PSMA-617 for PSMA PET Imaging

The implementation of theranostics in oncologic nuclear medicine has exhibited immense potential in improving patient outcomes in prostate cancer with the implementation of [ 68 Ga]Ga-PSMA-11 PET and [ 177 Lu]Lu-PSMA-617 into clinical practice. However, the correlation between radiopharmaceutical biodistributions seen with [ 68 Ga]Ga-PSMA-11 PET imaging and downstream [ 177 Lu]Lu-PSMA-617 therapy remains imperfect. This suggests that prostate cancer theranostics could potentially be further refined through the implementation of true theranostics, tandem pairs of diagnostic and therapeutic radiopharmaceuticals that utilize the same ligand and element, thus yielding identical pharmacokinetics. The radioscandiums are one such group of true theranostic radiopharmaceuticals. The radioscandiums consist of two β+ emitting scandium isotopes ( 43 Sc/ 44 Sc), as well as a β − emitting therapeutic isotope ( 47 Sc), which can all conjugate with PSMA-targeting PSMA-617. This potential has led to extensive investigations into the production of the radioscandiums as well as pre-clinical assessments with several ligands; however, there is a lack of literature extensively describing the complete synthesis of scandium radiopharmaceuticals. which therefore limits the accessibility of radioscandium research in theranostics. As such, this work aims to present an easily translatable protocol for the synthesis of [ 43 Sc]Sc-PSMA-617 from a [ 42 Ca]CaCO 3 starting material, including target formation, nuclear production via 42 Ca(d,n) 43 Sc reaction, chemical separation, radiolabeling, solvent reformulation, and target recycling.

62 RADIOLOGY AND NUCLEAR MEDICINE↗