Recent Program-Supported Publications

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.

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.

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.

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.

Abstract: Protactinium-230 (t_1/2 = 17.4 d) is the parent isotope of ²³⁰U (t_1/2 = 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.

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.

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).

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.).