6 Search Results

Extractive diglycolamide (DGA) resins are used in several state-of-the-art techniques for purifying ²²⁵Ac, a promising radiometal for targeted alpha therapy. Unfortunately, separation processes that rely on resins are often limited to slow flow rates, high elution volumes, and long processing times. Membrane adsorbers functionalized with DGA ligands are an alternative separation material that may overcome these challenges. This work presents (1) the synthesis of an aminated tetrahexyldiglycolamide ligand, (2) the covalent tethering of the ligand to electrospun poly(vinylbenzyl chloride) fiber mats, and (3) the adsorption and desorption of La(III) and ²²⁵Ac. Chemical and physical characterization supports the covalent tethering ofmore » the ligand to the fiber mat, as well as the preservation of the fiber surface area and porosity after functionalization. Equilibrium adsorption experiments were performed with stable La(III) and radioactive ²²⁵Ac. Trends in affinity are consistent between commercial resins and the synthesized membrane adsorbers; however, the Langmuir constants and the maximum binding capacity of the membrane adsorbers were generally lower than the resins. Despite these differences, the modeled selectivity for an equimolar solution of La(III)/²²⁵Ac in 10 M nitric acid is 57. Furthermore, ²²⁵Ac is rapidly desorbed from the fibers in 10 M nitric acid (<20 min). The La(III)/²²⁵Ac selectivity and rapid ²²⁵Ac desorption indicate this class of materials is promising for rapid radioanalytical separations.« less

²²⁵Ac-targeted α-radiotherapy is a promising approach to treating malignancies, including prostate cancer. However, α-emitting isotopes are difficult to image because of low administered activities and a low fraction of suitable γ-emissions. The in vivo generator ¹³⁴Ce/¹³⁴La has been proposed as a potential PET imaging surrogate for the therapeutic nuclides ²²⁵Ac and ²²⁷Th. In this report, we detail efficient radiolabeling methods using the ²²⁵Ac-chelators DOTA and MACROPA. These methods were applied to radiolabeling of prostate cancer imaging agents, including PSMA-617 and MACROPA-PEG₄-YS5, for evaluation of their in vivo pharmacokinetic characteristics and comparison to the corresponding ²²⁵Ac analogs. Methods: Radiolabeling was performedmore » by mixing DOTA/MACROPA chelates with ¹³⁴Ce/¹³⁴La in NH₄OAc, pH 8.0, at room temperature, and radiochemical yields were monitored by radio–thin-layer chromatography. In vivo biodistributions of ¹³⁴Ce-DOTA/MACROPA.NH₂ complexes were assayed through dynamic small-animal PET/CT imaging and ex vivo biodistribution studies over 1 h in healthy C57BL/6 mice, compared with free ¹³⁴CeCl₃. In vivo, preclinical imaging of ¹³⁴Ce-PSMA-617 and ¹³⁴Ce-MACROPA-PEG₄-YS5 was performed on 22Rv1 tumor–bearing male nu/nu-mice. Ex vivo biodistribution was performed for ¹³⁴Ce/²²⁵Ac-MACROPA-PEG₄-YS5 conjugates. Results: ¹³⁴Ce-MACROPA.NH₂ demonstrated near-quantitative labeling with 1:1 ligand-to-metal ratios at room temperature, whereas a 10:1 ligand-to-metal ratio and elevated temperatures were required for DOTA. Rapid urinary excretion and low liver and bone uptake were seen for ¹³⁴Ce/²²⁵Ac-DOTA/MACROPA. NH₂ conjugates in comparison to free ¹³⁴CeCl₃ confirmed high in vivo stability. An interesting observation during the radiolabeling of tumor-targeting vectors PSMA-617 and MACROPA-PEG₄-YS5—that the daughter ¹³⁴La was expelled from the chelate after the decay of parent ¹³⁴Ce—was confirmed through radio–thin-layer chromatography and reverse-phase high-performance liquid chromatography. Both conjugates, ¹³⁴Ce-PSMA-617 and ¹³⁴Ce-MACROPA-PEG₄-YS5, displayed tumor uptake in 22Rv1 tumor–bearing mice. The ex vivo biodistribution of ¹³⁴Ce-MACROPA.NH₂, ¹³⁴Ce-DOTA and ¹³⁴Ce-MACROPA-PEG₄-YS5 corroborated well with the respective ²²⁵Ac-conjugates. Conclusion: These results demonstrate the PET imaging potential for ¹³⁴Ce/¹³⁴La-labeled small-molecule and antibody agents. The similar ²²⁵Ac and ¹³⁴Ce/¹³⁴La-chemical and pharmacokinetic characteristics suggest that the ¹³⁴Ce/¹³⁴La pair may act as a PET imaging surrogate for ²²⁵Ac-based radioligand therapies.« less

Monte Carlo transport codes PHITS and MCNP6 were used to calculate the production cross sections of ^225,227Ac, ^227,229Th, ^223,225Ra, and ^229,230,231Pa via the bombardment of a ²³²Th target with energetic protons, deuterons, and α-particles. The incident projectile energies ranged between 10 and 800 MeV/nucleon. When possible, the predicted production cross sections were compared with the available experimental data and other predictions. Here, the degree of the codes’ abilities to match the measured data provides a qualitative assessment of the codes’ abilities to predict data from similar, but unmeasured, projectile/target systems. In addition, a comparison between calculated cross sections and datamore » may provide insight into possible improvements in the physics models employed by those transport codes.« less

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.more » 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.« less

Actinium-225 is a potential Targeted Alpha Therapy (TAT) isotope. It can be generated with high energy (≥ 100 MeV) 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 agreementmore » 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 (ΔG_aq) calculations confirm significantly higher selectivity of DGA based resins for Ln^III over Ac^III in the presence of nitrate. As a result, DFT calculations and experimental results reveal that Ac chemistry cannot be predicted from lanthanide behavior under comparable circumstances.« less

Actinium-225 and ²¹³Bi have been used successfully in targeted alpha therapy (TAT) in preclinical and clinical research. This paper is a continuation of research activities aiming to expand the availability of ²²⁵Ac. The high energy proton spallation reaction on natural thorium metal target has been utilized to produce millicurie quantities of ²²⁵Ac. The results of sixteen irradiation experiments of Th metal at beam energies between 78 and 200 MeV are summarized in this work. Irradiations have been conducted at Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL), while target dissolution and processing was carried out at Oak Ridgemore » National Laboratory (ORNL). Excitation functions for actinium and thorium isotopes as well as for some of the fission products are presented. The cross sections for production of ²²⁵Ac range from 3.6 to 16.7 mb in the incident proton energy range of 78 to 192 MeV. Based on these data, production of Curie quantities of 225Ac is possible by irradiating a 5.0 g cm^-2232Th target for 10 days in either BNL or LANL proton irradiation facilities.« less