Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes

Radchenko, Valery; Engle, Jonathan W.; Wilson, Justin J.; Maassen, Joel R.; Nortier, F.M.; Taylor, W. A.; Birnbaum, Eva R.; Hudston, Lisa A.; John, Kevin D.; Fassbender, Michael E.

doi:10.1016/j.chroma.2014.12.045

Cited by 92 publications

(59 citation statements)

References 20 publications

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“…Additionally, there had to be a method to remove the Lu III from Ac III after the experiment, so that the precious actinium sample could be recycled for future studies. Consistent with many actinium/lanthanide separation studies, 17,5,24,25,32−38 we observed that liquid/liquid extraction chromatography (branched DGA; Eichrom) was effective for purifying Ac III from Lu III . As an example, “proof-of-principle” experiments using stable Lu III (0.5 mg) spiked with a radioactive 173 Lu tracer [ t 1/2 = 1.37(1) y; 5.8 kBq; 3.6 × 10 11 atoms] 3 and short-lived 225 Ac [ t 1/2 = 10.0(1) d; 8.8 kBq; 1.1 × 10 10 atoms] demonstrated feasibility.…”

Section: Resultssupporting

confidence: 87%

“…Moreover, this procedure was successfully applied in recovering 227 Ac after the XAFS experiment. Although similar elution profiles were previously reported using trace quantities of actinium and lanthanides, 4,17,18,36,38−44 our separation demonstrated that the DGA process accommodated a large mass range. This spanned picogram (pg) to microgram (μg) quantities with successful separations both at the tracer level ( 225 Ac = 1.1 × 10 10 atoms; 173 Lu = 3.6 × 10 11 atoms) and using large masses ( 227 Ac = 7.4 × 10 4 kBq, 7.4 × 10 16 atoms, 2.8 × 10 –5 g; stable Lu = 1.7 × 10 18 atoms, 5.0 × 10 –4 g).…”

Section: Resultssupporting

confidence: 86%

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Synthesis and Characterization of the Actinium Aquo Ion

et al. 2017

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Metal aquo ions occupy central roles in all equilibria that define metal complexation in natural environments. These complexes are used to establish thermodynamic metrics (i.e., stability constants) for predicting metal binding, which are essential for defining critical parameters associated with aqueous speciation, metal chelation, in vivo transport, and so on. As such, establishing the fundamental chemistry of the actinium(III) aquo ion (Ac-aquo ion, Ac(H2O)x3+) is critical for current efforts to develop 225Ac [t1/2 = 10.0(1) d] as a targeted anticancer therapeutic agent. However, given the limited amount of actinium available for study and its high radioactivity, many aspects of actinium chemistry remain poorly defined. We overcame these challenges using the longer-lived 227Ac [t1/2 = 21.772(3) y] isotope and report the first characterization of this fundamentally important Ac-aquo coordination complex. Our X-ray absorption fine structure study revealed 10.9 ± 0.5 water molecules directly coordinated to the AcIII cation with an Ac–OH2O distance of 2.63(1) Å. This experimentally determined distance was consistent with molecular dynamics density functional theory results that showed (over the course of 8 ps) that AcIII was coordinated by 9 water molecules with Ac–OH2O distances ranging from 2.61 to 2.76 Å. The data is presented in the context of other actinide(III) and lanthanide(III) aquo ions characterized by XAFS and highlights the uniqueness of the large AcIII coordination numbers and long Ac–OH2O bond distances.

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Section: Resultssupporting

confidence: 87%

Section: Resultssupporting

confidence: 86%

Synthesis and Characterization of the Actinium Aquo Ion

et al. 2017

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“…In one study of the separation of actinium(II) from thorium(IV) and radium(II), thorium(IV) was eluted with citric acid from AG50W-X8 resin. The procedure did however include several other steps with the use of strong acids and extraction chromatography resin DGA (Eichrom) [266]. Cation exchange resins DOWEX 50W-X8, AG50W-X8 and Merk I have in another study been used for the sorption of calcium (II), barium(II) and radium(II) with desorption by the aid of tartrate, EDTA and citrate, but the pH (>8) was high for desorption of radium(II) and no separation of thorium(II) from radium(II) was studied [267].…”

Section: Selected Methods For Column Separation and Purification Of Tmentioning

confidence: 99%

Development of separation technology for the removal of radium-223 from decayed thorium-227 in drug formulations. Material screening and method development

Frenvik

Kristensen

Ryan

2015

Drug Development and Industrial Pharmacy

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Targeted thorium conjugates are currently being investigated as a new class of alpha-radiopharmaceuticals. The natural decay of thorium-227 ((227)Th) results in the ingrowth of radium-223 ((223)Ra). Consideration must, therefore, be given to define acceptable limits of (223)Ra in the drug product at the time of dose administration. By effective sequestration of (223)Ra, we aim to improve the radiochemical purity and extend the effective user window of drug products containing (227)Th. (223)Ra is the first progeny of (227)Th and the only one with a long half-life (days). We have, therefore, focused on the removal of this specific species since the progenies of (223)Ra will have a very limited lifetime in the formulation once (223)Ra is removed. In this study, we investigated a multitude of materials for their ability to reduce the (223)Ra level by: (1) passive diffusion or (2) by cartridge filtration on gravity columns. In addition, we probe the compatibility of these materials in the presence of antibody trastuzumab to assess the level of protein binding and estimate the quenching of radiolysis by binding of radionuclides. A screening matrix of organic and inorganic materials was established, i.e. strontium and calcium alginate gel beads, distearoyl phosphatidylglycerol (DSPG) liposomes, ceramic hydroxyapatite, Zeolite UOP type 4A and cation exchange resins AG50W-X8 and SOURCE 30S. First, passive diffusional uptake of (223)Ra by suspended materials present in the formulation was measured as a decrease in sample radioactivity after separation. Second, selected materials were packed on gravity columns in order to evaluate the efficiency of column separation versus diffusional adsorption. The retention of (223)Ra and (227)Th were characterized by measuring the radioactivity in the eluate and on the columns. Finally, the compatibility between trastuzumab, as a selected model antibody, and suspensions of the binding materials was analyzed during storage of the drug product in the presence of adsorbent. The formation of H2O2 was evaluated to measure the influence of radionuclide binding material on radiolysis in the formulation. All the materials bound (223)Ra by passive diffusional uptake ranging from 31% to 95% with DSPG liposomes demonstrating superiority at 95% efficiency. All materials suitable for assessment by gravity column filtration bound (223)Ra almost quantitatively (∼100%) and with minimal variation (relative standard deviation <1%). The uptake was significantly higher compared to passive diffusional uptake. Alginate gel beads, ceramic hydroxyapatite and SOURCE 30S reduced the antibody concentration in solution to 40-50% while the Zeolite UOP type 4A, AG50W-X8 resin and DSPG liposomes showed ≤10% reduction of antibody concentration. Ceramic hydroxyapatite significantly reduced H2O2 formed by radionuclide initiated radiolysis.

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“…More recently, research efforts have been undertaken by the US Department of Energy to achieve cyclotron-production of 225 Ac using high-energy proton irradiation of natural thorium targets (Radchenko et al, 2015a; Radchenko et al, 2015b; Weidner et al, 2012). However, 227 Ac contamination is a side-product of this irradiation (approximately ≈0.3%).…”

Section: Introductionmentioning

confidence: 99%

A Radium-223 microgenerator from cyclotron-produced trace Actinium-227

Abou

Pickett

Mattson

et al. 2017

Applied Radiation and Isotopes

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The alpha particle emitter Radium-223 dichloride (223RaCl2) has recently been approved for treatment of late-stage bone metastatic prostate cancer. There is considerable interest in studying this new agent outside of the clinical setting, however the supply of 223Ra is limited and expensive. We have engineered a 223Ra microgenerator using traces of 227Ac previously generated from cyclotron-produced 225Ac. Radiochemically pure 223RaCl2 was made, characterized, evaluated in vivo, and the source was recovered in high yield for regeneration of the microgenerator.

show abstract

Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes

Cited by 92 publications

References 20 publications

Synthesis and Characterization of the Actinium Aquo Ion

Synthesis and Characterization of the Actinium Aquo Ion

Development of separation technology for the removal of radium-223 from decayed thorium-227 in drug formulations. Material screening and method development

A Radium-223 microgenerator from cyclotron-produced trace Actinium-227

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