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.

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.

Cover of Molecules Journal

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


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


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.

Applied Radiation and Isotopes cover

Electron linear accelerator production and purification of scandium-47 from titanium dioxide targets

Abstract: The photonuclear production of no-carrier-added (NCA) 47Sc from solid NatTiO2 and the subsequent chemical processing and purification have been developed. Scandium-47 was produced by the 48Ti(γ,p)47Sc reaction with Bremsstrahlung photons produced from the braking of electrons in a high-Z (W or Ta) convertor. Production yields were simulated with the PHITS code (Particle and Heavy Ion Transport-code System) and compared to experimental results. Irradiated TiO2 targets were dissolved in fuming H2SO4 in the presence of Na2SO4 and 47Sc was purified using the commercially available Eichrom DGA resin. Typical 47Sc recovery yields were >90% with excellent specific activity for small batches (<185 MBq batches).

journal cover

Consensus nomenclature rules for radiopharmaceutical chemistry — Setting the record straight

Abstract: Over recent years, within the community of radiopharmaceutical sciences, there has been an increased incidence of incorrect usage of established scientific terms and conventions, and even the emergence of ‘self-invented’ terms. In order to address these concerns, an international Working Group on ‘Nomenclature in Radiopharmaceutical Chemistry and related areas’ was established in 2015 to achieve clarification of terms and to generate consensus on the utilisation of a standardised nomenclature pertinent to the field.

Upon open consultation, the following consensus guidelines were agreed, which aim to:

  • Provide a reference source for nomenclature good practice in the radiopharmaceutical sciences.
  • Clarify the use of terms and rules concerning exclusively radiopharmaceutical terminology, i.e. nuclear- and radiochemical terms, symbols and expressions.
  • Address gaps and inconsistencies in existing radiochemistry nomenclature rules.
  • Provide source literature for further harmonisation beyond our immediate peer group (publishers, editors, IUPAC, pharmacopoeias, etc.).