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.

Defining Processing Times for Accelerator Produced 225Ac and Other Isotopes from Proton Irradiated Thorium.

During the purification of radioisotopes, decay periods or time dependent purification steps may be required to achieve a certain level of radiopurity in the final product. Actinum-225 (Ac-225), Silver-111 (Ag-111), Astatine-211 (At-211), Ruthenium-105 (Ru-105), and Rhodium-105 (Rh-105) are produced in a high energy proton irradiated thorium target. Experimentally measured cross sections, along with MCNP6-generated cross sections, were used to determine the quantities of Ac-225, Ag-111, At-211, Ru-105, Rh-105, and other co-produced radioactive impurities produced in a proton irradiated thorium target at Brookhaven Linac Isotope Producer (BLIP). Ac-225 and Ag-111 can be produced with high radiopurity by the proton irradiation of a thorium target at BLIP.

Radiometric evaluation of diglycolamide resins for the chromatographic separation of actinium from fission product lanthanides.

Actinium-225 is a potential Targeted Alpha Therapy (TAT) isotope. It can be generated with high energy (≥ 100MeV) proton irradiation of thorium targets. The main challenge in the chemical recovery of 225Ac lies in the separation from thorium and many fission by-products most importantly radiolanthanides. We recently developed a separation strategy based on a combination of cation exchange and extraction chromatography to isolate and purify 225Ac. In this study, actinium and lanthanide equilibrium distribution coefficients and column elution behavior for both TODGA (N,N,N',N'-tetra-n-octyldiglycolamide) and TEHDGA (N,N,N',N'-tetrakis-2-ethylhexyldiglycolamide) were determined. Density functional theory (DFT) calculations were performed and were in agreement with experimental observations providing the foundation for understanding of the selectivity for Ac and lanthanides on different DGA (diglycolamide) based resins. The results of Gibbs energy (ΔGaq) calculations confirm significantly higher selectivity of DGA based resins for LnIII over AcIII in the presence of nitrate. DFT calculations and experimental results reveal that Ac chemistry cannot be predicted from lanthanide behavior under comparable circumstances.

Proton-induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/44Sc generator development.

Scandium-44g (half-life 3.97h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44gSc is the 44Ti/44gSc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44Ti isolation and purification. This study describes the production of a combined 175MBq (4.7mCi) batch yield of 44Ti in week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44Ti via anion exchange sorption in concentrated HCl results in a 44Tc/Sc separation factor of 102-103. A second, cation exchange based step in HCl media is then applied for 44Ti fine purification from residual Sc mass. In summary, this method yields a 90-97% 44Ti recovery with an overall Ti/Sc separation factor of ≥106.

Production scale purification of Ge-68 and Zn-65 from irradiated gallium metal.

Germanium-68 (Ge-68) is produced by proton irradiation of a gallium metal target, purified by organic extraction and used in a medical isotope generator to produce Gallium-68 PET imaging agents. The purpose of this work was to implement a production scale separation of Ge-68 and Zn-65 that does not use organic solvents and uses a limited number of columns. The current separation approach was modified to use AG1 resin and/or Sephadex(©) G25 with zinc spikes to purify Ge-68 with near quantitative recovery. The purified Ge-68 meets DOE specifications. Methods utilizing zinc spikes resulted in the purist Ge-68 produced at Brookhaven National Lab with no other impurities by ICP-OES. During process optimization approximately 2.5 Ci of Ge-68 was purified utilizing the different processing methods, and the material was sold to the Nuclear Medicine community between 2012-2013.

Tailoring medium energy proton beam to induce low energy nuclear reactions in 86SrCl2 for production of PET radioisotope 86Y.

This paper reports results of experiments at Brookhaven Linac Isotope Producer (BLIP) aiming to investigate effective production of positron emitting radioisotope (86)Y by the low energy (86)Sr(p,n) reaction. BLIP is a facility at Brookhaven National Laboratory designed for the proton irradiation of the targets for isotope production at high and intermediate proton energies. The proton beam is delivered by the Linear Accelerator (LINAC) whose incident energy is tunable from 200 to 66 MeV in approximately 21 MeV increments. The array was designed to ensure energy degradation from 66 MeV down to less than 20 MeV. Aluminum slabs were used to degrade the proton energy down to the required range. The production yield of (86)Y (1.2+/-0.1 mCi (44.4+/-3.7) MBq/µAh) and ratio of radioisotopic impurities was determined by assaying an aliquot of the irradiated (86)SrCl2 solution by gamma spectroscopy. The analysis of energy dependence of the (86)Y production yield and the ratios of radioisotopic impurities has been used to adjust degrader thickness. Experimental data showed substantial discrepancies in actual energy propagation compared to energy loss calculations.

Development of a large scale production of 67Cu from 68Zn at the high energy proton accelerator: closing the 68Zn cycle.

A number of research irradiations of (68)Zn was carried out at Brookhaven Linac Isotope Producer aiming to develop a practical approach to produce the radioisotope (67)Cu through the high energy (68)Zn(p,2p)(67)Cu reaction. Disks of enriched zinc were prepared by electrodeposition of (68)Zn on aluminum or titanium substrate and isolated in the aluminum capsule for irradition. Irradiations were carried out with 128, 105 and 92 MeV protons for at least 24h. After irradiation the disk was chemically processed to measure production yield and specific activity of (67)Cu and to reclaim the target material. The recovered (68)Zn was irradiated and processed again. The chemical procedure comprised BioRad cation exchange, Chelex-100 and anion exchange columns. Reduction of the oxidation degree of copper allowed for more efficient Cu/Co/Zn separation on the anion exchange column. No radionuclides other than copper isotopes were detected in the final product. The chemical yield of (67)Cu reached 92-95% under remote handling conditions in a hot box. Production yield of (67)Cu averaged 29.2 µCi/[µA-h×g (68)Zn] (1.08MBq/[µA-h×g (68)Zn]) in 24h irradiations. The best specific activity achieved was 18.6 mCi/µg (688.2 MBq/µg).

Activation of natural Hf and Ta in relation to the production of 177Lu.

The isotope (177)Lu is used in nuclear medicine and biology for in vivo applications as a radioactive label of various targeting agents. To extend the availability of no-carrier added (177)Lu, we investigated the feasibility of its production in a proton accelerator. Tantalum and Hf targets were irradiated and chemically processed to determine the radioisotope yield and cross-sections. The largest cross-sections (approximately 20 mb) were found for the Hf target at 195 MeV; however, the presence of co-produced Lu isotopes may limit the product applications. The results are in good agreement with theoretical data calculated using computer codes MCNPX and ORIGEN2S. Production of relevant medical isotopes such as (167)Tm and (169)Yb from the above targets is discussed as well.