Elucidating the coordination chemistry of the radium ion for targeted alpha therapy.

The coordination chemistry of Ra2+ is poorly defined, hampering efforts to design effective chelators for 223Ra-based targeted alpha therapy. Here, we report the complexation thermodynamics of Ra2+ with the biomedically-relevant chelators DOTA and macropa. Our work reveals the highest affinity chelator to date for Ra2+ and advances our understanding of key factors underlying complex stability and selectivity for this underexplored ion.

Nuclear data for reactor production of 131Ba and 133Ba.

The newest radioisotope for brachytherapy treatment of prostate cancer is 131Cs (t1/2 = 9.69 d, 100% EC). Generated via electron capture decay of 131Ba (t1/2 = 11.6 d, 100% EC), 131Cs has been used in brachytherapy for prostate cancer since 2004. The 131Ba parent is produced through neutron capture of enriched 130Ba in a nuclear reactor. For large-scale production of 131Ba, an accurate knowledge of production and burnup cross sections of 131Ba are essential. In this paper, we report two group cross sections (thermal and resonance integrals) for 130Ba and 131Ba and a new measure of the half-life of 131Ba. Targets consisting of milligram quantities of enriched 130Ba (∼35%) were irradiated in Oak Ridge National Laboratory's High Flux Isotope Reactor at thermal and resonance neutron fluxes of (1.9-2.1) × 1015 and (5.8-7.0) × 1013 neutrons·cm-2 s-1, respectively, for durations ranging from 3 to 26 days. In addition, cadmium covered samples of 130Ba were irradiated for 1 hour at 12.6% full reactor power (10.7 MW). The yield of 131Ba approaches a saturation value of ∼60 GBq (∼1.6 Ci) per mg of 130Ba for 20 days irradiation at a thermal neutron flux of 1.8 × 1015 n·s-1·cm-2, with a thermal/epithermal ratio of ∼30. Under the above experimental conditions, the two group cross sections of 130Ba are 6.9 ±â€¯0.5 b (thermal, σ0) and 173 ±â€¯7 b (resonance, I0). These values represent the sum of cross sections to metastable and ground states of 131Ba. For 131Ba, the empirically measured thermal cross section is 200 ±â€¯50 b assuming an I0/σ0 of 10. This cross section is reported for the first time. Further, the half-life of 131Ba was remeasured to be 11.657 ±â€¯0.008 d. Lastly, this study also resulted in the co-production of 133Ba (t1/2 = 10.52 y, 100% EC). The experimental yield of 133Ba is ∼370 MBq (∼10 mCi) per mg of 132Ba (thin target) for one cycle irradiation in the High Flux Isotope Reactor, and measured two-group 132Ba cross sections are 7.2 ±â€¯0.2 b and 39.9 ±â€¯1.3 b. These values also represent the sum of cross sections to metastable and ground states of 133Ba.

Measurement of neutron capture cross section of 187W for production of 188W.

Tungsten-188 (t1/2 = 69.4 d) is routinely produced by double neutron capture using highly enriched 186W target, 186W(n,γ)187W(n,γ)188W reaction, at the ORNL 85 MWt High Flux Isotope Reactor. While the thermal neutron cross section for the first reaction, 186W(n,γ)187W, is well known, the single reported 64 b cross-section for the second reaction, 187W(n,γ)188W, cannot be validated by experimental results that yield lower than expected activities of 188W. In this study, we report a new value for the thermal neutron capture cross section of 187W. After confirming the neutron capture cross section of 186W (σ0 = 37.8 ±â€¯1.8 b for thermal and I0 = 476 ±â€¯25 b for resonance integrals with σ0/I0 = 12.6 ±â€¯0.4) in two short irradiations, longer irradiations (1-10 d) were performed to obtain a value of 6.5 ±â€¯0.8 b for the σ0 of 187W, which is lower than the adopted value by a factor of 10. Due to the short half-life of 187W (t1/2 = 23.7 d), the σ0 for 187W was obtained empirically by comparing the 188W experimental yields with the theoretical yields generated by code IsoChain and varying the 187W cross section while keeping all other parameters constant.

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.

Reactor production of promethium-147.

In this paper, we describe the 147Pm production yields and level of impurities from several targets that consisted of milligram quantities of highly enriched 146Nd oxide irradiated at the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory for durations ranging from 24 to 180 h. A comparison between theoretical and experimental data are also presented, and attempts were made to empirically evaluate the neutron capture cross-sections of 41.3-d 148mPm and 5.4-d 148gPm. For a one-cycle irradiation (~24 days), 147Pm yield reaches a maximum value of 101.8 MBq/mg (2.75 mCi/mg) at 60 days after the end of bombardment. Because of large neutron capture cross-sections of 147Pm, the yield of 147Pm does not significantly increase with longer irradiation. Our estimates of the thermal neutron capture cross-section and resonance integral for 146Nd at 1.48 ±â€¯0.05 b and 2.56 ±â€¯0.25 b, respectively, were consistent with the reported values. The effective neutron capture cross-section of 147Pm to 148mPm was 53.3 ±â€¯2.7 b-a factor of 2 lower than the 98.7 ±â€¯6.5 b calculated from reported cross-sections. The measured σeff to the ground state (5.37-d 148gPm) was 82.0 ±â€¯4.1 b; ~34% lower than the value of 139 ±â€¯10 b calculated from reported cross-sections. In this work, we also describe the development of a chemical process based on extraction and ion-exchange chromatography for separation of 147Pm from milligram quantities of 146Nd and other impurities. Sequential separation of Pm from the Nd target and from other radioisotopic impurities (153Gd and 154&155Eu, 192Ir, and 60Co) was achieved using a LN extraction resin in HCl media followed by further purification of Pm from 60Co and 192Ir using a low cross-linking cation exchange resin. Based on these data, we estimated that two rounds of purification under our experimental conditions can provide a mass separation factor of >104 between Pm and Nd. Our data indicate that curie quantities of 147Pm with suitable chemical and radioisotopic purity for applications in beta voltaic batteries can be produced by irradiating gram quantities of highly enriched 146Nd in the flux trap of HFIR for one cycle.

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.

Simultaneous Separation of Actinium and Radium Isotopes from a Proton Irradiated Thorium Matrix.

A new method has been developed for the isolation of 223,224,225Ra, in high yield and purity, from a proton irradiated 232Th matrix. Herein we report an all-aqueous process using multiple solid-supported adsorption steps including a citrate chelation method developed to remove >99.9% of the barium contaminants by activity from the final radium product. A procedure involving the use of three columns in succession was developed, and the separation of 223,224,225Ra from the thorium matrix was obtained with an overall recovery yield of 91 ± 3%, average radiochemical purity of 99.9%, and production yields that correspond to physical yields based on previously measured excitation functions.