Recent Program-Supported Publications

The U.S. Department of Energy Isotope Program (DOE IP) supports research and development of novel methods to produce isotopes of national interest or of new or improved technologies that foster enhanced isotope production. The following research manuscripts acknowledge the DOE IP for their funding contributions.

Note: This is not a comprehensive list of publications related to the DOE IP. Our list attempts to capture all publications from 2019 and beyond.

Radiolysis and radionuclide production in a flowing-water target during fast 40Ca20+ irradiation.

Radiolysis and radionuclide production in a flowing-water target during fast 40Ca20+ irradiation.

A flowing-water target was irradiated with a 140 MeV/u, 8 nA 40Ca20+ beam to test the feasibility of isotope harvesting at the upcoming Facility for Rare Isotope Beams. Among other radionuclides, 2.6(2)E-6 48Cr and 5.6(5)E-6 28 Mg nuclei were formed for every impingent 40Ca and were collected through ion exchange. Radiolysis-induced molecular hydrogen evolved from the target at an initial rate of 0.91(9) H2 molecules per 100 eV of beam energy deposited. No radiation-accelerated corrosion of the target material was observed.

ScienceDirect Mar 2020

Novel design and diagnostics improvements for increased production capacity and improved reliability at the Los Alamos Isotope Production Facility

The Isotope Production Facility (IPF) at Los Alamos National Laboratory (LANL) is used to produce an array of isotopes for medical, global security, and research applications with an intense beam of protons supplied by the linear accelerator at the Los Alamos Neutron Science Center (LANSCE). An Accelerator Improvement Project (AIP) was recently conducted at IPF to improve facility reliability and reduce programmatic risk while increasing general isotope production capacity and flexibility. This was accomplished through the installation of an improved beam window assembly, more robust beam diagnostics, an active and adjustable collimator, and a new beam rastering system. This paper will highlight the four exciting innovations and how they were designed, validated, and installed in parallel as well as the significant operational advantages they provide to IPF. Key experiments and the increased currents achieved in routine production runs demonstrating the enhanced capability from the AIP will be presented. The most notable capability enhancements include irradiations with beam currents ranging from 100 nA experimental runs up to 300 μA on routine production targets and utilization of a range of cylindrical target diameters.

 

Nature cover

Development of an autonomous solvent extraction system to isolate astatine-211 from dissolved cyclotron bombarded bismuth targets

Cyclotron-produced astatine-211 (211At) shows tremendous promise in targeted alpha therapy (TAT) applications due to its attractive half-life and its 100% α-emission from nearly simultaneous branched alpha decay. Astatine-211 is produced by alpha beam bombardment of naturally monoisotopic bismuth metal (209Bi) via the (α, 2n) reaction. In order to isolate the small mass of 211At (specific activity = 76 GBq·µg−1) from several grams of acid-dissolved Bi metal, a manual milliliter-scale solvent extraction process using diisopropyl ether (DIPE) is routinely performed at the University of Washington. As this process is complex and time-consuming, we have developed a fluidic workstation that can perform the method autonomously.

Isotope harvesting at FRIB: additional opportunities for scientific discovery

Isotope harvesting at FRIB: additional opportunities for scientific discovery

The upcoming Facility for Rare Isotope Beams (FRIB) at Michigan State University provides a new opportunity to access some of the world's most specialized scientific resources: radioisotopes. An excess of useful radioisotopes will be formed as FRIB fulfills its basic science mission of providing rare isotope beams. In order for the FRIB beams to reach high-purity, many of the isotopes are discarded and go unused. If harvested, the unused isotopes could enable new research for diverse applications ranging from medical therapy and diagnosis to nuclear security. Given that FRIB will have the capability to create about 80% of all possible atomic nuclei, harvesting at FRIB will provide a fast path for access to a vast array of isotopes of interest in basic and applied science investigations. To fully realize this opportunity, infrastructure investment is required to enable harvesting and purification of otherwise unused isotopes. An investment in isotope harvesting at FRIB will provide a powerful resource for development of crucial isotope applications. In 2010, the United States Department of Energy Office of Science, Nuclear Physics, sponsored the first 'Workshop on Isotope Harvesting at FRIB', convening researchers from diverse fields to discuss the scientific impact and technical feasibility of isotope harvesting. Following the initial meeting, a series of biennial workshops was organized. At the fourth workshop, at Michigan State University in 2016, the community elected to prepare a formal document to present their findings. This report is the output of the working group, drawing on contributions and discussions with a broad range of scientific experts.

Cover of Molecules Journal

Optimization of Cation Exchange for the Separation of Actinium-225 from Radioactive Thorium, Radium-223 and Other Metals

Abstract

Actinium-225 (225Ac) can be produced with a linear accelerator by proton irradiation of a thorium (Th) target, but the Th also underdoes fission and produces 400 other radioisotopes. No research exists on optimization of the cation step for the purification. The research herein examines the optimization of the cation exchange step for the purification of 225Ac. The following variables were tested: pH of load solution (1.5–4.6); rinse steps with various concentrations of HCl, HNO3, H2SO4, and combinations of HCl and HNO3; various thorium chelators to block retention; MP50 and AG50 resins; and retention of 20–45 elements with different rinse sequences. The research indicated that HCl removes more isotopes earlier than HNO3, but that some elements, such as barium and radium, could be eluted with ≥2.5 M HNO3. The optimal pH of the load solution was 1.5–2.0, and the optimized rinse sequence was five bed volumes (BV) of 1 M citric acid pH 2.0, 3 BV of water, 3 BV of 2 M HNO3, 6 BV of 2.5 M HNO3 and 20 BV of 6 M HNO3. The sequence recovered >90% of 225Ac with minimal 223Ra and thorium present.

Beam Interaction with Materials and Atoms Journal Cover

Natural nickel as a proton beam energy monitor for energies ranging from 15 to 30 MeV

Abstract

The degradation of proton beam energy within a target stack was monitored via product nuclide ratios at the Los Alamos Isotope Production Facility (LANL-IPF). Nuclear reaction channels employed as energy monitors included NatNi(p,x)57Co and NatNi(p,x)57Ni. Natural nickel foils (thicknesses 0.025 mm) were used to determine proton beam energies ranging from 15 to 30 MeV. Energy values were estimated from a fitted 57Ni/57Co production activity ratio curve, which, in turn, was calculated from formation cross section data. Isotope production yields in the low energy “C” slot at LANL-IPF are very sensitive to beam energy, and differences of several MeV can translate into a drastic effect on overall production yields and radiochemical purity. Proton energies determined in this target stack position using nickel foils will serve as a basis to optimize radionuclide production in terms of product yield maximization and by-product minimization.

ACS Central Science

Large-Scale Production of Te-119m and Sb-119 for Radiopharmaceutical Applications

Recent efforts in using radioactive isotopes in vivo have provided creative solutions to numerous global health problems. (1−18) Consider that positron and X-ray emissions from isotopes like 18F, 82Rb, 68Ga, 99mTc, and 201Tl now find widespread use in imaging technologies to treat millions of patients worldwide each year. (19−22) Equally exciting is the potential for harnessing particles emitted during nuclear decay to treat disease, e.g., cancer, bacterial infections, viral infections (like HIV), and other nonmalignant disorders (such as degenerative skeletal pain, Graves orbitopathy, and Gorham Stout syndrome).(23,24) Of numerous radionuclides that show promise, 119Sb is particularly interesting. This isotope decays by emitting K-edge and conversion electrons, collectively called Auger electrons. The 119Sb attraction originates from the low energy (∼20 keV) of these Auger electrons, which results in short biological path lengths (∼10 μm) that are comparable with the diameter of many human cells. (25) Hence, therapeutic targeting with 119Sb provides a unique opportunity to deliver a lethal dose of radiation to a targeted diseased cell while leaving the adjacent healthy tissue unharmed. (26−30) The potential for patient recovery along with little to no hematological toxicity (no negative side-effects) is extraordinary in comparison to nontargeted treatment methods, i.e., nontargeted chemotherapy.

Current Radiopharmaceuticals Journal Cover

The production of Ac-225

Alpha radiation therapy is essential in radiotherapy for cancer patients. The radio-isotopes of actinium and bismuth which are 225Ac and 213Bi, respectively, are considered to be the most effective alpha radiation emitters. These isotopes can be used for radiolabeled isotopes in clinical trials or as alpha radiation sources in linear accelerators.

Global supplies of these isotopes are insufficient to fulfill the clinical demands for therapy which is projected to increase with a growing demand for radiopharmaceuticals in research and medicine. Procurement of these isotopes is done through a combination of public and private funding, involving government agencies which handle decaying nuclear fuel and private chemical processing plants which isolate the elements. The health hazards associated with high radiation levels also pose a significant logistical challenge, which adds to the costs of such efforts. Current production technologies have yet to prove themselves sustainable enough to provide a complete solution.

This review published in Current Radiopharmaceuticals gives information about current supplies of 225Ac. Readers will find details about the historical and current supply of actinium, the current production routes (as a function of radioactive decay of parent elements and the nature of particle bombardment to produce larger quantities of the isotopes) and a summary of the current situation in relation to isotope generating supply chains. The reviewers conclude that while most 225Ac production options are uniformly costly, 2 production routes relying on the irradiation of 226Ra/227Ac and 232Th targets produce higher yields which may serve the needs of an increased demand in actinium due to expanding medical programs and related clinical trials.

Analytical Chemistry cover

Separation of Protactinium Employing Sulfur-Based Extraction Chromatographic Resins

Abstract: Protactinium-230 (t1/2 = 17.4 d) is the parent isotope of 230U (t1/2 = 20.8 d), a radionuclide of interest for targeted alpha therapy (TAT). Column chromatographic methods have been developed to separate no-carrier-added 230Pa from proton irradiated thorium targets and accompanying fission products. Results reported within demonstrate the use of novel sulfur bearing chromatographic extraction resins for the selective separation of protactinium. The recovery yield of 230Pa was 93 ± 4% employing a R3P=S type commercially available resin and 88 ± 4% employing a DGTA (diglycothioamide) containing custom synthesized extraction chromatographic resin. The radiochemical purity of the recovered 230Pa was measured via high purity germanium γ-ray spectroscopy to be >99.5% with the remaining radioactive contaminant being 95Nb due to its similar chemistry to protactinium. Measured equilibrium distribution coefficients for protactinium, thorium, uranium, niobium, radium, and actinium on both the R3P=S type and the DGTA resin in hydrochloric acid media are reported, to the best of our knowledge, for the first time.

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Chromatographic separation of the theranostic radionuclide 111Ag from a proton irradiated thorium matrix

Abstract: Column chromatographic methods have been developed to separate no-carrier-added 111Ag from proton irradiated thorium targets and associated fission products as an ancillary process to an existing 225Ac separation design. Herein we report the separation of 111Ag both prior and subsequent to 225Ac recovery using CL resin, a solvent impregnated resin (SIR) that carries an organic solution of alkyl phosphine sulfides (R3P = S) and alkyl phosphine oxides (R3P = O). The recovery yield of 111Ag was 93 ± 9% with a radiochemical purity of 99.9% (prior) and 87 ± 9% with a radiochemical purity of 99.9% (subsequent to) 225Ac recovery. Both processes were successfully performed with insignificant impacts on 225Ac yields or quality. Measured equilibrium distribution coefficients for silver and ruthenium (a residual contaminant) on CL resin in hydrochloric and nitric acid media are reported, to the best of our knowledge, for the first time. Additionally, measured cross sections for the production of 111Ag and 110mAg for the 232Th(p,f)110m,111Ag reactions are reported within.