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.

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.

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.