Michael E. Fassbender

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

Actinium-225 (t1/2=9.92d) is an α-emitting radionuclide with nuclear properties well-suited for use in targeted alpha therapy (TAT), a powerful treatment method for malignant tumors. Actinium-225 can also be utilized as a generator for (213)Bi (t1/2 45.6 min), which is another valuable candidate for TAT. Actinium-225 can be produced via proton irradiation of thorium metal; however, long-lived (227)Ac (t1/2=21.8a, 99% β(-), 1% α) is co-produced during this process and will impact the quality of the final product. Thus, accurate assays are needed to determine the (225)Ac/(227)Ac ratio, which is dependent on beam energy, irradiation time and target design. Accurate actinium assays, in turn, require efficient separation of actinium isotopes from both the Th matrix and highly radioactive activation by-products, especially radiolanthanides formed from proton-induced fission. In this study, we introduce a novel, selective chromatographic technique for the recovery and purification of actinium isotopes from irradiated Th matrices. A two-step sequence of cation exchange and extraction chromatography was implemented. Radiolanthanides were quantitatively removed from Ac, and no non-Ac radionuclidic impurities were detected in the final Ac fraction. An (225)Ac spike added prior to separation was recovered at ≥ 98%, and Ac decontamination from Th was found to be ≥ 10(6). The purified actinium fraction allowed for highly accurate (227)Ac determination at analytical scales, i.e., at (227)Ac activities of 1-100 kBq (27 nCi to 2.7 μCi).

Proton-induced cross sections relevant to production of 225Ac and 223Ra in natural thorium targets below 200 MeV

Cross sections for (223,)(225)Ra, (225)Ac and (227)Th production by the proton bombardment of natural thorium targets were measured at proton energies below 200 MeV. Our measurements are in good agreement with previously published data and offer a complete excitation function for (223,)(225)Ra in the energy range above 90 MeV. Comparison of theoretical predictions with the experimental data shows reasonable-to-good agreement. Results indicate that accelerator-based production of (225)Ac and (223)Ra below 200 MeV is a viable production method.

225Ac and 223Ra production via 800 MeV proton irradiation of natural thorium targets

Cross sections for the formation of (225,227)Ac, (223,225)Ra, and (227)Th via the proton bombardment of natural thorium targets were measured at a nominal proton energy of 800 MeV. No earlier experimental cross section data for the production of (223,225)Ra, (227)Ac and (227)Th by this method were found in the literature. A comparison of theoretical predictions with the experimental data shows agreement within a factor of two. Results indicate that accelerator-based production of (225)Ac and (223)Ra is a viable production method.

Proton irradiation parameters and chemical separation procedure for the bulk production of high-specific-activity 186gRe using WO3 targets

Abstract Rhenium-186g (T1/2= 89.2 h) is a β− emitter suitable for therapeutic applications. Current production methods rely on reactor production via 185Re(n,γ) which results in low specific activities, thereby limiting its use. Production by p,d activation of enriched 186W results in a 186gRe product with a higher specific activity, allowing it to be used for targeted therapy with limited receptors. A test target consisting of pressed, sintered natWO3 was proton irradiated at Los Alamos (LANL-IPF) to evaluate product yield and impurities, irradiation parameters and wet chemical Re recovery for proof-of-concept for bulk production of 186gRe. We demonstrated isolation of 186gRe in 97% yield from irradiated natWO3 targets within 12 h of end of bombardment (EOB) via an alkaline dissolution followed by anion exchange. The recovery process has potential for automation, and WO3 can be easily recycled for recurrent irradiations. A 186gRe batch yield of 42.7 ± 2.2 μCi/μAh or 439 ± 23 MBq/C was obtained after 24 h in an 18.5 μA proton beam. The target entrance energy was determined to be 15.6 MeV. The specific activity of 186gRe at EOB was measured to be 1.9 kCi (70.3 TBq) mmol−1, which agrees well with the result of a previous 185,186mRe co-production EMPIRE and TALYS modeling study assuming similar conditions. Utilizing enriched 186WO3, we anticipate that a proton beam of 250 μA for 24 h will provide batch yields of 256 mCi (9.5 GBq) of 186gRe at EOB with specific activities even higher than 1.9 kCi (70.3 TBq) mmol−1, suitable for therapy applications.

Ac, La, and Ce radioimpurities in 225Ac produced in 40–200 MeV proton irradiations of thorium

Abstract Accelerator production of 225Ac addresses the global supply deficiency currently inhibiting clinical trials from establishing 225Acs therapeutic utility, provided that the accelerator product is of sufficient radionuclidic purity for patient use. Two proton activation experiments utilizing the stacked foil technique between 40 and 200 MeV were employed to study the likely co-formation of radionuclides expected to be especially challenging to separate from 225Ac. Foils were assayed by nondestructive γ-spectroscopy and by α-spectroscopy of chemically processed target material. Nuclear formation cross sections for the radionuclides 226Ac and 227Ac as well as lower lanthanide radioisotopes 139Ce, 141Ce, 143Ce, and 140La whose elemental ionic radii closely match that of actinium were measured and are reported. The predictions of the latest MCNP6 event generators are compared with measured data, as they permit estimation of the formation rates of other radionuclides whose decay emissions are not clearly discerned in the complex spectra collected from 232Th(p,x) fission product mixtures.

Cross sections from proton irradiation of thorium at 800 MeV

Nuclear formation cross sections are reported for 65 nuclides produced from 800-MeV proton irradiation of thorium foils. These data are useful as benchmarks for computational predictions in the ongoing process of theoretical code development and also to the design of spallation-based radioisotope production currently being considered for multiple radiotherapeutic pharmaceutical agents. Measured data are compared with the predictions of three MCNP6 event generators and used to evaluate the potential for 800-MeV productions of radioisotopes of interest for medical radiotherapy. In only a few instances code predictions are discrepant from measured values by more than a factor of two, demonstrating satisfactory predictive power across a large mass range. Similarly, agreement between measurements presented here and those previously reported is good, lending credibility to predictions of target yields and radioimpurities for high-energy accelerator-produced radionuclides.

Proton beam simulation with MCNPX/CINDER'90: Germanium metal activation estimates below 30 MeV relevant to the bulk production of arsenic radioisotopes

Germanium metal targets encapsulated in Nb shells were irradiated in a proton beam. Proton and secondary neutron beam fluences as well as radionuclide activity formation were modeled using MCNPX in combination with CINDER90. Targets were chemically processed using distillation and anion exchange. Good agreement between the measured radiochemical yields and MCNPX/CINDER90 estimates was observed. A target of pentavalent (73,74)As radioarsenic for neutron activation studies was prepared.

Large scale accelerator production of 225Ac: Effective cross sections for 78–192 MeV protons incident on 232Th targets

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 targets has been utilized to produce millicurie quantities of 225Ac. The results of sixteen irradiation experiments of thorium metal at beam energies between 78 and 192MeV 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 Ridge 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 16.7mb in the incident proton energy range of 78-192MeV. Based on these data, production of curie quantities of 225Ac is possible by irradiating a 5.0gcm-2 232Th target for 10 days in either BNL or LANL proton irradiation facilities.

Radiochemical study of re/w adsorption behavior on a strongly basic anion exchange resin

Abstract Rhenium-186g is a radionuclide with a high potential for therapeutic applications. It emits therapeutic β− particles accompanied by low energy γ-rays, which allows for in-vivo tracking of the radiolabeled compound and dosimetry estimates. The current reactor production pathway 185Re(n, γ)186gRe produces low specific activity 186gRe, thereby limiting its therapeutic application. Work is underway to develop an accelerator-based, charged particle induced production method for high specific activity 186gRe from targets of enriched 186W. To optimize the chemical 186gRe recovery method, batch studies have been performed to characterize the adsorption behavior of Re and W on a strongly basic anion exchange resin. An in-depth physicochemical profile was developed for the interaction of Re with resin material, which showed the reaction to be endothermic and spontaneous. Basic (NaOH) and acidic (HNO3) matrices were used to determine the equilibrium distribution coefficients for Re and W. The resin exhibits the best affinity for Re at slightly basic conditions and little affinity above moderately acidic concentrations. Tungsten has low affinity for the resin above moderately basic concentrations. A study was performed to examine the effect of W concentration on Re adsorption, which showed that even a high ionic WO42– strength of up to 1.9 mol kg–1 does not significantly compromise ReO4– retention on the resin.

Formation cross-sections and chromatographic separation of protactinium isotopes formed in proton-irradiated thorium metal

Abstract Targeted alpha therapy (TAT) is a treatment method of increasing interest to the clinical oncology community that utilizes α-emitting radionuclides conjugated to biomolecules for the selective killing of tumor cells. Proton irradiation of thorium generates a number of α-emitting radionuclides with therapeutic potential for application via TAT. In particular, the radionuclide 230Pa is formed via the 232Th(p, 3n) nuclear reaction and partially decays to 230U, an α emitter which has recently received attention as a possible therapy nuclide. In this study, we estimate production yields for 230Pa and other Pa isotopes from proton-irradiated thorium based on cross section measurements. We adopt existing methods for the chromatographic separation of protactinium isotopes from proton irradiated thorium matrices to combine and optimize them for effective fission product decontamination.